Role of the CD19 and CD21/35 receptor complex in innate immunity, host defense and autoimmunity

Advances in Experimental Medicine and Biology

Volumn 560, Issue , 2005, Pages 125-139

  Haas, Karen M ^b   Tedder, Thomas F ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CD19 ANTIGEN; COMPLEMENT COMPONENT C3B RECEPTOR; COMPLEMENT COMPONENT C3D; COMPLEMENT COMPONENT C3D RECEPTOR; COMPLEMENT;

ANTIGEN EXPRESSION; ANTIGEN FUNCTION; ANTIGEN STRUCTURE; AUTOIMMUNITY; B LYMPHOCYTE; BACTERIAL IMMUNITY; CELL STRUCTURE; CONFERENCE PAPER; ENCAPSULATION; HOST RESISTANCE; MOLECULAR MODEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; ANIMAL; BACTERIUM; BIOLOGICAL MODEL; GENETICS; IMMUNOLOGY; INNATE IMMUNITY; PHYSIOLOGY; REVIEW;

ANIMALS; ANTIGENS, CD19; AUTOIMMUNITY; BACTERIA; COMPLEMENT SYSTEM PROTEINS; IMMUNITY, NATURAL; MICE; MODELS, BIOLOGICAL; RECEPTORS, COMPLEMENT 3B; RECEPTORS, COMPLEMENT 3D;

EID: 20344391186     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/0-387-24180-9_16     Document Type: Conference Paper

References (119)

1. T. F. Tedder, Response-regulators of B lymphocyte signaling thresholds provide a context for antigen receptor signal transduction. Semin. Immunol. 10, 259-265 (1998).
2. S. Sato, D. A. Steeber, P. J. Jansen and T. F. Tedder, CD19 expression levels regulate B lymphocyte development: human CD19 restores normal function in mice lacking endogenous CD19. J. Immunol. 158, 4662-4669 (1997).
3. S. Sato, N. Ono, D. A. Steeber, D. S. Pisetsky and T. F. Tedder, CD19 regulates B lymphocyte signaling thresholds critical for the development of B-1 lineage cells and autoimmunity. J. Immunol. 157, 4371-4378 (1996).
4. T. F. Tedder and C. M. Isaacs, Isolation of cDNAs encoding the CD19 antigen of human and mouse B lymphocytes: A new member of the immunoglobulin superfamily. J. Immunol. 143, 712-717 (1989).
5. L.-J. Zhou, D. C. Ord, A. L. Hughes and T. F. Tedder, Structure and domain organization of the CD19 antigen of human, mouse and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain. J. Immunol. 147, 1424-1432 (1991).
6. I. Krop, A. L. Shaffer, D. T. Fearon and M. S. Schlissel, The signaling activity of murine CD19 is regulated during B cell development. J. Immunol. 157, 48-56 (1996).
7. A. W. Boyd, K. C. Anderson, A. S. Freedman, D. C. Fisher, B. Slaughenhoupt, S. F. Schlossman and L. M. Nadler, Studies of in vitro activation and differentiation of human B lymphocytes. I. Phenotypic and functional characterization of the B cell population responding to anti-Ig antibody. J. Immunol. 134, 1516-1523 (1985).
8. L. E. Bradbury, G. S. Kansas, S. Levy, R. L. Evans and T. F. Tedder, The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules. J. Immunol. 149, 2841-2850 (1992).
9. S. Levy, S. C. Todd and H. T. Maecker, CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu. Rev. Immunol. 16, 89-110 (1998).
10. H. T. Maecker and S. Levy Normal lymphocyte development but delayed humoral immune response in CD81-null mice. J. Exp. Med. 185, 1505-1510 (1997).
11. T. Miyazaki, U. Muller and K. S. Campbell, Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. EMBO J. 16, 4217-4225 (1997).
12. E. N. Tsitsikov, J.-C. Gutierrez-Ramos and R. S. Geha, Impaired CD19 expression and signaling, enhanced antibody response to type II T-independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc. Natl. Acad. Sci. USA 94, 10844-10849 (1997).
13. T. Shoham, R. Rajapaksa, C. Boucheix, E. Rubinstein, J. C. Poe, T. F. Tedder and S. Levy, The tetraspanin CD81 regulates the expression of CD19 during B cell development in a postendoplasmic reticulum compartment. J. Immunol. 171, 4062-4072 (2003).
14. G. A. Deblandre, O. P. Marinx, S. S. Evans, S. Majjaj, O. Leo, D. Caput, G. A. Huez and M. G. Wathelet, Expression cloning of an interferon-inducible 17-kDa membrane protein implicated in the control of cell growth. J. Biol. Chem. 270, 23860-23866 (1995).
15. L. E. Bradbury, V. S. Goldmacher and T. F. Tedder, The CD19 signal transduction complex of B lymphocytes: deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu-13. J. Immunol. 151, 2915-2927 (1993).
16. A. K. Matsumoto, D. R. Martin, R. H. Carter, L. B. Klickstein, J. M. Abeam and D. T. Fearon, Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. J. Exp. Med. 178, 1407-1417 (1993).
17. C. J. van Noesel, A. C. Lankester, G. M. van Schijndel and R. A. van Lier, The CR2/CD19 complex on human B cells contains the src-family kinase Lyn. Int. Immunol. 5, 699-705 (1993).
18. F. M. Uckun, A. L. Burkhardt, L. Jarvis, X. Jun, B. Stealey, I. Dibirdik, D. E. Myers, L. Tuel-Ahlgren and J. B. Bolen, Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny. J. Biol. Chem. 268, 21172-21184 (1993).
19. N. J. Chalupny, S. B. Kanner, G. L. Schieven, S. Wee, L. K. Gilliland, A. Aruffo and J. A. Ledbetter, Tyrosine phosphorylation of CD19 in pre-B and mature B cells. EMBO J. 12, 2691-2696 (1993).
20. M. Fujimoto, J. C. Poe, P. J. Jansen, S. Sato and T. F. Tedder CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation. J. Immunol. 162, 7088-7094 (1999).
21. M. Fujimoto, Y. Fujimoto, J. C. Poe, P. J. Jansen, C. A. Lowell, A. L. DeFranco and T. F. Tedder, CD19 regulates Src-family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 13, 47-57 (2000).
22. M. Hasegawa, M. Fujimoto, J. C. Poe, D. A. Steeber, C. A. Lowell and T. F. Tedder, A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. J. Immunol. 167, 2469-2478 (2001).
23. M. Fujimoto, J. C. Poe, M. Inaoki and T. F. Tedder, CD19 regulates B lymphocyte responses to transmembrane signals. Semin. Immunol. 10, 267-277 (1998).
24. P. A. Zipfel, M. Grove, K. Blackburn, M. Fujimoto, T. F. Tedder and A. M. Pendergast, The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19. J. Immunol. 165, 6872-6879 (2000).
25. A. Cherukuri, P. C. Cheng, H. W. Sohn and S. K. Pierce, The CD19/CD21 complex functions to prolong B cell antigen receptor signaling from lipid rafts. Immunity 14, 169-179 (2001).
26. M. Fujimoto, A. P. Bradney, J. C. Poe, D. A. Steeber and T. F. Tedder, Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop. Immunity 11, 191-200 (1999).
27. S. Sato, P. J. Jansen and T. F. Tedder, CD19 and CD22 reciprocally regulate Vav tyrosine phosphorylation during B lymphocyte signaling. Proc. Natl. Acad. Sci., USA 94, 13158-13162 (1997).
28. W. K. Weng, L. Jarvis and T. W. LeBien, Signaling through CD19 activates vav/mitogen-activated protein kinase pathway and induces formation of a CD19/vav/phosphatidylinositol 3-kinase complex in human B cell precursors. J. Biol. Chem. 269, 32514-32521 (1994).
29. D. A. Tuveson, R. H. Carter, S. P. Soltoff and D. T. Fearon, CD19 of B cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science 260, 986-989 (1993).
30. 2+ mobilization. J. Exp. Med. 186, 1897-1910 (1997).
31. G. M. Doody, D. D. Balladeau, E. Clayton, A. Hutchings, R. Berland, S. McAdam, P. J. Leibson and M. Turner, Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes. EMBO J. 19, 6173-6184 (2000).
32. S. R. Brooks, X. Li, E. J. Volanakis and R. H. Carter, Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Daudi human B cells: clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. J. Immunol. 164, 3123-3131 (2000).
33. J. C. Poe, M. Fujimoto, P. J. Jansen, A. S. Miller and T. F. Tedder, CD22 forms a quaternary complex with SHIP, Grb2 and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux. J. Biol. Chem. 275, 17420-17427 (2000).
34. R. H. Carter and D. T. Fearon, CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. Science 256, 105-107 (1992).
35. P. W. Dempsey, M. E. D. Allison, S. Akkaraju, C. C. Goodnow and D. T. Fearon, C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271, 348-350 (1996).
36. R. M. Tooze, G. M. Doody and D. T. Fearon, Counterregulation by the coreceptors CD19 and CD22 of MAP kinase activation by membrane immunoglobulin. Immunity 7, 59-67 (1997).
37. T. F. Tedder, M. Inaoki and S. Sato, The CD19/21 complex regulates signal transduction thresholds governing humoral immunity and autoimmunity. Immunity 6, 107-118 (1997).
38. P. Engel, L.-J. Zhou, D. C. Ord, S. Sato, B. Koller and T. F. Tedder, Abnormal B lymphocyte development, activation and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3, 39-50 (1995).
39. L.-J. Zhou, H. M. Smith, T. J. Waldschmidt, R. Schwarting, J. Daley and T. F. Tedder, Tissue-specific expression of the human CD19 gene in transgenic mice inhibits antigen-independent B lymphocyte development. Mol. Cell. Biol. 14, 3884-3894 (1994).
40. R. C. Rickert, K. Rajewsky and J. Roes, Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 376, 352-355 (1995).
41. S. Sato, D. A. Steeber and T. F. Tedder, The CD19 signal transduction molecule is a response regulator of B-lymphocyte differentiation. Proc. Natl. Acad. Sci. USA 92, 11558-11562 (1995).
42. S. Sato, A. S. Miller, M. C. Howard and T. F. Tedder, Regulation of B lymphocyte development and activation by the CD19/CD21/CD81/Leu 13 complex requires the cytoplasmic domain of CD19. J. Immunol. 159, 3278-3287 (1997).
43. A. Pezzutto, B. Dorken, P. S. Rabinovitch, J. A. Ledbetter, G. Moldenhauer and E. A. Clark, CD19 monoclonal antibody HD37 inhibits anti-immunoglobulin-induced B cell activation and proliferation. J. Immunol. 138, 2793-2799 (1987).
44. T. B. Barrett, G. L. Shu, K. E. Draves, A. Pezzutto and E. A. Clark, Signaling through CD19, Fc receptors or transforming growth factor-β: each inhibits the activation of resting human B cells differently. Eur. J. Immunol. 20, 1053-1059 (1990).
45. R. E. Callard, K. P. Rigley, S. H. Smith, S. Thurstan and J. G. Shields, CD19 regulation of human B cell responses. B cell proliferation and antibody secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein depending on the stimulating signal used. J. Immunol. 148, 2983-2987 (1992).
46. D. T. Fearon and R. H. Carter, The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu. Rev. Immunol. 13, 127-149 (1995).
47. C. J. M. van Noesel, A. C. Lankester and R. A. W. van Lier, Dual antigen recognition by B cells. Immunol. Today 14, 8-11 (1993).
48. J. M. Ahearn, M. B. Fischer, D. Croix, S. Goerg, M. Ma, J. Xia, X. Zhou, R. G. Howard, T. L. Rothstein and M. C. Carroll, Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 4, 251-262 (1996).
49. H. Molina, V. M. Holers, B. Li, Y.-F. Fang, S. Mariathasan, J. Goellner, J. Strauss-Schoenberger, R. W. Karr and D. D. Chaplin, Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc. Natl. Acad. Sci. USA 93, 3357-3361 (1996).
50. M. Hasegawa, M. Fujimoto, J. C. Poe, D. A. Steeber and T. F. Tedder, CD19 can regulate B lymphocyte signal transduction independent of complement activation. J. Immunol. 167, 3190-3200 (2001).
51. T. F. Tedder, L. T. Clement and M. D. Cooper Discontinuous expression of a membrane antigen (HB-7) during B lymphocyte differentiation. Tissue Antigens 24, 140-149 (1984).
52. K. Takahashi, Y. Kozono, T. J. Waldschmidt, D. Berthiaume, R. J. Quigg, A. Baron and V. M. Holers, Mouse complement receptors type 1 (CR1; CD35) and type 2 (CR2; CD21). Expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. J. Immunol. 159, 1557-1569 (1997).
53. H. Molina, T. Kinoshita, K. Inoue, J.-C. Carel and V. M. Holers, A molecular and immunochemical characterization of mouse CR2. Evidence for a single gene model of mouse complement receptors 1 and 2. J. Immunol. 145, 2974-2983 (1990).
54. M. D. Moore, N. R. Cooper, B. F. Tack and G. R. Nemerow, Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes. Proc. Natl. Acad. Sci. USA. 84, 9194-9198. (1987).
55. J. J. Weis, D. T. Fearon, L. B. Klickstein, W. W. Wong, S. A. Richards, A. d. Kops, J. A. Smith and J. H. Weis, Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. Proc. Natl. Acad. Sci. USA 83, 5639-5643. (1986).
56. J. C. Carel, B. L. Myones, B. Frazier and V. M. Holers, Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization and viral infection. J. Biol. Chem. 265, 12293-12297 (1990).
57. D. T. Fearon and M. C. Carroll, Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu. Rev. Immunol. 18, 393-422 (2000).
58. J. M. Aheam and D. T. Fearon, Structure and function of the complement receptors, CR1 (CD35) and CR2 (CD21). Adv. Immunol. 46, 183-219 (1989).
59. K. M. Haas, M. Hasegawa, D. A. Steeber, J. C. Poe, M. D. Zabel, C. B. Bock, D. R. Karp, D. E. Briles, J. H. Weis and T. F. Tedder, Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses. Immunity 17, 713-723 (2002).
60. -/- Mice: Enhanced affinity maturation but impaired antibody persistence. J. Immunol. 164, 4522-4532 (2000).
61. -/- mice is rescued by adjuvants without improvement in germinal center development. J. Immunol. 165, 3119-3127 (2000).
62. A. W. Griffioen, G. T. Rijkers, P. Janssens-Korpela and B. J. Zegers, Pneumococcal polysaccharides complexed with C3d bind to human B lymphocytes via complement receptor type 2. Infect. Immun. 59, 1839-1845. (1991).
63. T. Manser, K. M. Tumas-Brundage, L. P. Casson, A. M. Giusti, S. Hande, E. Notidis and K. A. Vora, The roles of antibody variable region hypermutation and selection in the development of the memory B-cell compartment. Immunol. Rev. 162, 183-196 (1998).
64. J. Pryjma, J. H. Humphrey and G. G. Klaus, C3 activation and T-independent B cell stimulation. Nature 252, 505-506. (1974).
65. O. G. Pozdnyakova, H.K. Guttormsen, F. N. Lalani, M. C. Carroll and D. L. Kasper, Impaired antibody response to group B streptococcal type III capsular polysaccharide in C3- and complement receptor 2-deficient mice. J Immunol. 170, 84-90. (2003).
66. M. J. Peset Llopis, G. Harms, M. J. Hardonk and W. Timens, Human immune response to pneumococcal polysaccharides: complement-mediated localization preferentially on CD21-positive splenic marginal zone B cells and follicular dendritic cells. J. Allergy Clin. Immunol. 97, 1015-1024 (1996).
67. R. Guinamard, M. Okigaki, J. Schlessinger and J. V. Ravetch, Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral responses. Nature Immunol. 1, 31-36 (2000).
68. S. E. Henson, D. Smith, S. A. Boackle, V. M. Holers and D. R. Karp, Generation of recombinant human C3dg tetramers for the analysis of CD21 binding and function. J. Immunol. Methods 258, 97-109. (2001).
69. W. Timens, A. Boes, T. Rozeboom-Uiterwijk and S. Poppema, Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J. Immunol. 143, 3200-3206. (1989).
70. A. Cariappa, M. Tang, C. Parng, E. Nebelitskiy, M. Carroll, K. Georgopoulos and S. Pillai, The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 14, 603-615. (2001).
71. J. E. Figueroa and P. Densen, Infectious diseases associated with complement deficiencies. Clin. Microbiol. Rev. 4, 359-395. (1991).
72. L. A. Burman, R. Norrby and B. Trollfors, Invasive pneumococcal infections: incidence, predisposing factors, and prognosis. Rev. Infect. Dis. 7, 133-142. (1985).
73. I. D. Riley and R. M. Douglas, An epidemiologic approach to pneumococcal disease. Rev. Infect. Dis. 3, 233-245. (1981).
74. M. Botto and M. J. Walport, Hereditary deficiency of C3 in animals and humans. Int. Rev. Immunol. 10, 37-50 (1993).
75. J. A. Winkelstein, The role of complement in the host's defense against Streptococcus pneumoniae. Rev. Infect. Dis. 3, 289-298. (1981).
76. E. J. Brown, S. W. Hosea, C. H. Hammer, C. G. Burch and M. M. Frank, A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J. Clin. Invest. 69, 85-98. (1982).
77. G. J. Noel, S. L. Katz and P. J. Edelson, The role of C3 in mediating binding and ingestion of group B streptococcus serotype III by murine macrophages. Pediatr. Res. 30, 118-123. (1991).
78. M. S. Borzy, A. Gewurz, L. Wolff, D. Houghton and E. Lovrien, Inherited C3 deficiency with recurrent infections and glomerulonephritis. Am. J. Dis. Child. 142, 79-83. (1988).
79. E. J. Brown, S. W. Hosea and M. M. Frank, The role of complement in the localization of pneumococci in the splanchnic reticuloendothelial system during experimental bacteremia. J. Immunol. 126, 2230-2235. (1981).
80. A. Circolo, G. Garnier, W. Fukuda, X. Wang, T. Hidvegi, A. J. Szalai, D. E. Briles, J. E. Volanakis, R. A. Wetsel and H. R. Colten, Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology 42, 135-149. (1999).
81. Y. Fang, C. Xu, Y.-X. Fu, V. M. Holers and H. Molina, Expression of complement receptors 1 and 2 on follicular dendritic cells is necessary for the generation of a strong antigen-specific IgG response. J. Immunol. 160, 5273-5279 (1998).
82. J. Arvieux, H. Yssel and M. G. Colomb, Antigen-bound C3b and C4b enhance antigen-presenting cell function in activation of human T-cell clones. Immunology 65, 229-235. (1988).
83. S. A. Boackle, V. M. Holers and D. R. Karp CD21 augments antigen presentation in immune individuals. Eur. J. Immunol. 27, 122-129 (1997).
84. S. A. Boackle, M. A. Morris, V. M. Holers and D. R. Karp, Complement opsonization is required for presentation of immune complexes by resting peripheral blood B cells. J. Immunol. 161, 6537-6543. (1998).
85. B. P. Thornton, V. Vetvicka and G. D. Ross, Natural antibody and complement-mediated antigen processing and presentation by B lymphocytes. J. Immunol. 152, 1727-1737. (1994).
86. A. Cherukuri, P. C. Cheng and S. K. Pierce, The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J. Immunol. 167, 163-172. (2001).
87. F. Martin, A. M. Oliver and J. F. Kearney, Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14, 617-629. (2001).
88. high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells. J. Immunol. 162, 7198-7207 (1999).
89. J. C. Poe, M. Hasegawa and T. F. Tedder, CD19, CD21 and CD22: multifaceted response regulators of B lymphocyte signal transduction. Int. Rev. Immunol. 20, 739-762 (2001).
90. R. M. Perlmutter, D. Hansburg, D. E. Briles, R. A. Nicolotti and J. M. Davie, Subclass restriction of murine anti-carbohydrate antibodies. J. Immunol. 121, 566-572. (1978).
91. J. McLay, E. Leonard, S. Petersen, D. Shapiro, N. S. Greenspan and J. R. Schreiber, Gamma-3 gene-disrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides. II. Increased susceptibility to fatal pneumococcal sepsis due to absence of anti-polysaccharide IgG3 is corrected by induction of anti-polysaccharide IgG1. J. Immunol. 168, 3437-3443. (2002).
92. D. E. Briles, W. H. Benjamin, Jr., W. J. Huster and B. Posey, Genetic approaches to the study of disease resistance: with special emphasis on the use of recombinant inbred mice. Curr. Top. Microbiol. Immunol. 124, 21-35 (1986).
93. P. G. Shackelford, S. J. Nelson, A. T. Palma and M. H. Nahm, Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity. J. Immunol. 140, 3200-3205. (1988).
94. T. W. Kuijpers, R. S. Weening and T. A. Out, IgG subclass deficiencies and recurrent pyogenic infections: unresponsiveness against bacterial polysaccharide antigens. Allergol. Immunopathol. 20, 28-34. (1992).
95. N. S. Greenspan and L. J. Cooper, Cooperative binding by mouse IgG3 antibodies: implications for functional affinity, effector function, and isotype restriction. Springer Semin. Immunopathol. 15, 275-291 (1993).
96. H. Wardemann, T. Boehm, N. Dear and R. Carsetti, B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen. J. Exp. Med. 195, 771-780 (2002).
97. + B cells. Immunol. Rev. 137, 91-118 (1994).
98. T. M. Ross, Y. Xu, T. D. Green, D. C. Montefiori and H. L. Robinson, Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins. AIDS Res. and Human Retroviruses 17, 829-835 (2001).
99. T. D. Green, D. C. Montefiori and T. M. Ross, Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by using the molecular adjuvant C3d. J. Virology 77, 2046-2055 (2003).
100. J. A. Mitchell, T. D. Green, R. A. Bright and T. M. Ross, Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins. Vaccine 21, 902-914 (2003).
101. T. D. Green, B. R. Newton, P. Rota, Y. Xu, H. L. Robinson and T. M. Ross, Immune responses in mice to measles hemagglutin-C3d DNA vaccinations. Vaccine 20, 242-248 (2002).
102. T. M. Ross, Y. Xu, R. A. Bright and H. L. Robinson, C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza challenge. Nature Immunol. 1, 127-131 (2000).
103. I. Watanabe, T. M. Ross, S. I. Tamura, T. Ichinohe, S. Ito, H. Takahashi, H. Sawa, J. Chiba, T. Kurata, T. Sata and H. Hasegawa, Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin. Vaccine 21, 4532-4538. (2003).
104. S. T. Test, J. Mitsuyoshi, C. C. Connolly and A. H. Lucas, Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide. Infect. Immun. 69, 3031-3040. (2001).
105. R. H. Carter, M. O. Spycher, Y. C. Ng, R. Hoffman and D. T. Fearon, Synergistic interaction between complement receptor type 2 and membrane IgM on B lymphocytes. J. Immunol. 141, 457-463 (1988).
106. J. D. Fingeroth, M. A. Benedict, D. N. Levy and J. L. Strominger, Identification of murine complement receptor type 2. Proc. Natl. Acad. Sci. USA 86, 242-246 (1989).
107. K. M. Haas, F. R. Toapanta, J. A. Oliver, J. C. Poe, J. H. Weis, D. R. Karp, J. F. Bower, T. M. Ross and T. F. Tedder, C3d functions as a molecular adjuvant in the absence of CD21/35 expression, (submitted).
108. F. R. Vogel Improving vaccine performance with adjuvants. Clinical Infectious Diseases 30 Suppl 3, S266-270 (2000).
109. M. Bennett and T. Leanderson, Was it there all the time? Scand. J. of Immunol. 57, 499-505 (2003).
110. S. Sato, M. Hasegawa, M. Fujimoto, T. F. Tedder and K. Takehara, Quantitative genetic variation in CD19 expression correlates with autoimmunity in mice and humans. J. Immunol. 165, 6635-6643 (2000).
111. Y. Okano Antinuclear antibody in systemic sclerosis (scleroderma). Rheum. Dis. Clin. North Am. 22, 709-735 (1996).
112. E. Saito, M. Fujimoto, M. Hasegawa, K. Komura, Y. Hamaguchi, Y. Kaburagi, T. Nagaoka, K. Takehara, T. F. Tedder and S. Sato, CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse. J Clin. Invest 109, 1453-1462 (2002).
113. S. A. Boackle, V. M. Holers, X. Chen, G. Szakonyi, D. R. Karp, E. K. Wakeland and L. Morel, Cr2, a candidate gene in the murine Sle1c lupus susceptibility locus, encodes a dysfunctional protein. Immunity 15, 775-785. (2001).
114. A. P. Prodeus, S. Goerg, L. M. Shen, O. O. Pozdnyakova, L. Chu, E. M. Alicot, C. C. Goodnow and M. C. Carroll, A critical role for complement in maintenance of self-tolerance. Immunity 9, 721-731 (1998).
115. M. Carroll, The role of complement in B cell activation and tolerance. Adv. Immunol. 74, 61-88 (2000).
116. Z. Chen, S. B. Koralov and G. Kelsoe, Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2. J. Exp. Med. 192, 1339-1351 (2000).
117. J. P. Atkinson, in: Systemic Lupus Erythematosus. edited by R. G. Lahita (Churchill Livingston, Edinburgh; 1992), pp. 87-102.
118. 2+ responses: A role for Lyn sequestration in extinguishing negative regulation. J. Biol. Chem. 276, 44820-44827 (2001).
119. L. Chakravarty, M. D. Zabel, J. J. Weis and J. H. Weis, Depletion of Lyn kinase from the BCR complex and inhibition of B cell activation by excess CD21 ligation. Intl. Immunol. 14, 139-146 (2002).