Regulation of plasma-cell development

Nature Reviews Immunology

Volumn 5, Issue 3, 2005, Pages 230-242

  Shapiro Shelef, Miriam ^a   Calame, Kathryn Calame ^a  

^a Columbia Univ Coll Phys/Surgs ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR;

CELL DIFFERENTIATION; CELL MIGRATION; EFFECTOR CELL; GENE CONTROL; IMMUNOGLOBULIN PRODUCTION; MEMORY CELL; PLASMA CELL; PRIORITY JOURNAL; REVIEW;

ANIMALS; B-LYMPHOCYTES; BONE MARROW CELLS; CELL DIFFERENTIATION; CELL MOVEMENT; CELL PROLIFERATION; GERMINAL CENTER; HUMANS; MODELS, IMMUNOLOGICAL; PLASMA CELLS; SPLEEN;

EID: 14944362858     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1572     Document Type: Review

References (132)

1. Busslinger, M. Transcriptional control of early B cell development. Annu. Rev. Immunol. 22, 55-79 (2004).
2. Krangel, M. S. Gene segment selection in V(D)J recombination: accessibility and beyond. Nature Immunol. 4, 624-630 (2003).
3. Ohashi, P. S. & DeFranco, A. L. Making and breaking tolerance. Curr. Opin. Immunol. 14, 744-759 (2002).
4. Hardy, R. R. & Hayakawa, K. B cell development pathways. Annu. Rev. Immunol. 19, 595-621 (2001).
5. Chung, J. B., Silverman, M. & Monroe, J. G. Transitional B cells: step by step towards immune competence. Trends Immunol. 24, 343-349 (2003).
6. Pillia, S., Cariappa, A. & Moran, S. T. Marginal zone B cells. Annu. Rev. Immunol. 20 Oct 2004 (doi: 10.1146/annurev.immunol.23.021704.115728).
7. Lopes-Carvalho, T. & Kearney, J. F. Development and selection of marginal zone B cells. Immunol. Rev. 197, 192-205 (2004).
8. Tanigaki, K. et al. Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nature Immunol. 3, 443-450 (2002).
9. Oliver, A. M., Martin, F., Gartland, G. L., Carter, R. H. & Kearney, J. F. Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. Eur. J. Immunol. 27, 2366-2374 (1997).
10. 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).
11. Jacob, J., Kassir, R. & Kelsoe, G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. I. The architecture and dynamics of responding cell populations. J. Exp. Med. 173, 1165-1175 (1991).
12. Smith, K. G., Hewitson, T. D., Nossal, G. J. & Tarlinton, D. M. The phenotype and fate of the antibody-forming cells of the splenic foci. Eur. J. Immunol. 26, 444-448 (1996).
13. McHeyzer-Williams, L. J., Driver, D. J. & McHeyzer-Williams, M. G. Germinal center reaction. Curr. Opin. Hematol. 8, 52-59 (2001).
14. McHeyzer-Williams, M. G. B cells as effectors. Curr. Opin. Immunol. 15, 354-361 (2003).
15. Manser, T. Textbook germinal centers? J. Immunol. 172, 3369-3375 (2004).
16. Bishop, G. A. & Hostager, B. S. Signaling by CD40 and its mimics in B cell activation. Immunol. Res. 24, 97-109 (2001).
17. Kim, C. H. et al. Unique gene expression program of human germinal center T helper cells. Blood 104, 1952-1960 (2004).
18. Crotty, S., Kersh, E. N., Cannons, J., Schwartzberg, P. L. & Ahmed, R. SAP is required for generating long-term humoral immunity. Nature 421, 282-287 (2003).
19. Barrington, R. A., Pozdnyakova, O., Zafari, M. R., Benjamin, C. D. & Carroll, M. C. B lymphocyte memory: role of stromal cell complement and FcγRIIB receptors. J. Exp. Med. 196, 1189-1199 (2002).
20. McHeyzer-Williams, M. G. & Ahmed, R. B cell memory and the long-lived plasma cell. Curr. Opin. Immunol. 11, 172-179 (1999).
21. Maruyama, M., Lam, K. P. & Rajewsky, K. Memory B-cel persistence is independent of persisting immunizing antigen. Nature 407, 636-642 (2000).
22. Tangye, S. G., Avery, D. T., Deenick, E. K. & Hodgkin, P. D. Intrinsic differences in the proliferation of naive and memory human B cells as a mechanism for enhanced secondary immune responses. J. Immunol. 170, 686-694 (2003).
23. Bernasconi, N. L., Traggial, E. & Lanzavecchia, A. Maintenance of serological memory by potydonal activation of human memory B cells. Science 298, 2199-2202 (2002). This paper showed that bystander T-cell help and CpG oligodeoxynucleotides can activate human memory B cells in an antigen-independent manner.
24. - memory B cell compartment. J. Exp. Med. 191, 1149-1166 (2000).
25. Bell, J. & Gray, D. Antigen-capturing cells can masquerade as memory B cells. J. Exp. Med. 197, 1233-1244 (2003).
26. O'Connor, B. P., Cascalho, M. & Noelle, R. J. Short-lived and long-lived bone marrow plasma cells are derived from a novel precursor population. J. Exp. Med. 195, 737-745 (2002).
27. Shapiro-Shelef, M. et al. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory cells. Immunity 19, 607-620 (2003). In this study, mice with a B-cell-specific deletion of the gene that encodes BLIMP1 were created, and it was shown that BLIMP1 is required for plasma-cell formation and immunoglobulin secretion.
28. Hasbold, J., Corcoran, L. M., Tarlinton, D. M., Tangye, S. G. & Hodgkin, P. D. Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation. Nature Immunol. 5, 55-63 (2004). In this study, a division-tracking dye and stimulation of B cells in vitro were used, and it was shown that, at each cell division, there is a probability of plasmacytic differentiation.
29. Tangye, S. G. & Hodgkin, P. D. Divide and conquer: the importance of cell division in regulating B-cell responses. Immunology 112, 509-520 (2004).
30. Nutt, S. L., Eberhard, D., Horcher, M., Rolink, A. G. & Busslinger, M. Pax5 determines the identity of B cells from the beginning to the end of B-lymphopoiesis. Int. Rev. Immunol. 20, 65-82 (2001).
31. Lin, K. I., Angelin-Duclos, C., Kuo, T. C. & Calame, K. Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells to immunoglobulin M-secreting plasma cells. Mol. Cell. Biol. 22, 4771-4780 (2002).
32. Horcher, M., Souabni, A. & Busslinger, M. Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis. immunity 14, 779-790 (2001).
33. Gonda, H, et al. The balance between Pax5 and Id2 activities is the key to AID gene expression. J. Exp. Med. 198, 1427-1437 (2003).
34. Reimold, A. M. et al. Transcription factor B cell lineage-specific activator protein regulates the gene for human X-box binding protein 1. J. Exp. Med. 183, 393-401 (1996).
35. Rinkenberger, J. L., Wallin, J. J., Johnson, K. W. & Koshland, M. E. An interleukin-2 signal relieves BSAP (Pax5)-mediated repression of the immunoglobulin J chain gene. Immunity 5, 377-386 (1996).
36. Singh, M. & Birshtein, B. K. NF-HB (BSAP) is a repressor of the murine immunoglobulin heavy-chain 3′ α enhancer at early stages of B-cell differentiation. Mol. Cell. Biol. 13, 3611-3622 (1993).
37. Shatter, A. L., Peng, A. & Schlissel, M. S. In vivo occupancy of the κ light chain enhancers in primary pro- and pre-B cells: a model for κ locus activation. Immunity 6, 131-143 (1997).
38. Lin, L., Gerth, A. J. & Peng, S. L. Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor. J. Exp. Med. 200, 115-122 (2004).
39. Cattorerti, G. et al. BCL-6 protein is expressed in germinal-center B cells. Blood 86, 45-53 (1995).
40. Dent, A. L., Shatter, A. L., Yu, X., Allman, D. & Staudt, L. M. Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science 276, 589-592 (1997).
41. Shaffer, A. L. et al. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 13, 199-212 (2000). In this study, microarray analyses were used to identify direct targets of BCL-6, including the gene encoding BLIMP1.
42. Fearon, D. T., Manders, P. M. & Wagner, S. D. Bcl-6 uncouples B lymphocyte proliferation from differentiation. Adv. Exp. Med. Biol. 512, 21-28 (2002).
43. Tunyaplin, C. et al. Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation. J. Immunol. 173, 1158-1165 (2004).
44. Vasanwala, F. H., Kusam, S., Toney, L. M. & Dent, A. L. Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene. J. Immunol. 169, 1922-1929 (2002).
45. Reljic, R., Wagner, S. D., Peakman, L. J. & Fearon, D. T. Suppression of signal transducer and activator of transcription 3-dependent B lymphocyte terminal differentiation by BCL-6. J. Exp. Med. 192, 1841-1848 (2000).
46. Phan, R. T. & Dalla-Favera, R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature 432, 635-639 (2004).
47. Fujita, N. et al. MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell 119, 75-86 (2004). This paper showed that MTA3 is required for BCL-6 activity and that, when both MTA3 and BCL-6 are expressed by plasmacytomas, the immunoglobulin-secretion phenotype can be reversed.
48. Muto, A. et al. The transcriptional programme of antibody class switching involves the repressor Bach2. Nature 429, 566-571 (2004). This paper showed that BACH2 is required for the germinal-centre reaction and that it might inhibit plasmacytic differentiation.
49. Turner, C. A. Jr, Mack, D. H. & Davis, M. M. Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells. Cell 77, 297-306 (1994).
50. Angelin-Duclos, C., Cattoretti, G., Lin, K. I. & Calame, K. Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J. Immunol. 165, 5462-5471 (2000).
51. + B cells secrete immunoglobulin.
52. Lin, Y., Wong, K. & Calame, K. Repression of c-myc transcription by Blimp-1, an inducer of terminal B cell differentiation. Science 276, 596-599 (1997).
53. Shaffer, A. L. et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51-62 (2002). In this study, microarray analyses of human B-cell lines that ectopically express BLIMP1 allowed the identification of multiple genes that are regulated by BLIMP1. These could be divided into three categories on the basis of their function: repression of proliferation, induction of immunoglobulin secretion and repression of B-cell functions.
54. Shaffer, A. L. et al. XBP1 acts downstream of Blimp-1 to expand the secretory apparatus, promote organelle biogenesis, and increase protein synthesis during plasma cell differentetion. Immunity 21, 81-93 (2004).
55. Sciammas, R. & Davis, M. M. Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation. J. Immunol. 172, 5427-5440 (2004).
56. Reimold, A. M. et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature 412, 300-307 (2001). In this study, recombination-activating gene 1 (RAG1)-deficient blastocyst complementation was used to identify the transcriptional activator XBP1 as the first transcriptional regulator known to be required for plasma-cell formation.
57. Mittrucker, H. W. et al. Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 275, 540-543 (1997).
58. Falini, B. et al. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. Blood 95, 2084-2092 (2000).
59. Eisenbeis, C. F., Singh, H. & Storb, U. Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptions activator. Genes Dev, 9, 1377-1387 (1995).
60. Pongubala, J. M. & Atchison, M. L. PU.1 can participate in an active enhancer complex without its transcriptional activation domain. Proc. Natl Acad. Sci. USA 94, 127-132 (1997).
61. Allman, D. et al. BCL-6 expression during B-cell activation. Blood 87, 5257-5268 (1996).
62. Niu, H., Ye, B. H. & Dalla-Favera, R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 12, 1953-1961 (1998).
63. Muto, A. et al. Identification of Bach2 as a B-cell-specific partner for small Maf proteins that negatively regulate the immunoglobulin heavy chain gene 3′ enhancer. EMBO J. 17, 5734-5743 (1998).
64. 2-co-stimulated B lymphocytes. Eur. J. Immunol. 26, 268-271 (1996).
65. Snapper, C. M., Kehry, M. R., Castle, B. E. & Mond, J. J. Multivalent, but not divalent, antigen receptor cross-linkers synergize with CD40 ligand for induction of Ig synthesis and class switching in normal murine B cells. A redefinition of the TI-2 vs T cell-dependent antigen dichotomy. J. Immunol. 154, 1177-1187 (1995).
66. H cells control plasma cell production in vivo. Immunity 20, 231-242 (2004).
67. Gantner, F. et al. CD40-dependent and -independent activation of human tonsil B cells by CpG oligodeoxynucleotides. Eur. J. Immunol. 33, 1576-1585 (2003).
68. Takeda, K. & Akira, S. TLR signaling pathways. Semin. Immunol. 16, 3-9 (2004).
69. Piskurich, J. F. et al. BLIMP-1 mediates extinction of major histocompatibiity class II transactivator expression in plasma cells. Nature Immunol. 1, 526-532 (2000).
70. Wen, X. Y. et al. Identification of c-myc promoter-binding protein and X-box binding protein 1 as interleukin-6 target genes in human multiple myeloma cells. Int. J. Oncol. 15, 173-178 (1999).
71. Ozaki, K. et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J. Immunol. 173, 5361-5371 (2004).
72. Fearon, D. T., Manders, P. & Wagner, S. D. Arrested differentiation, the self-renewing memory lymphocyte, and vaccination. Science 293, 248-250 (2001).
73. Singh, M. & Birshtein, B. K. Concerted repression of an immunoglobulin heavy-chain enhancer, 3′α(hs1,2). Proc. Natl Acad. Sci. USA 93, 4392-4397 (1996).
74. H promoter/HS1,2 enhancer-linked transgene in late B cell development. Mol. Immunol. 37, 889-899 (2000).
75. Casellas, R. et al. OcaB is required for normal transcription and V(D)J recombination of a subset of immunoglobulin κ genes. Cell 110, 575-585 (2002).
76. Peterson, M. L., Bertolino, S. & Davis, F. An RNA polymerase pause site is associated with the immunoglobulin μs poly(A) site. Mol. Cell. Biol. 22, 5606-5615 (2002).
77. Veraldi, K. L. et al. hnRNP F influences binding of a 64-kilodalton subunit of cleavage stimulation factor to mRNA precursors in mouse B cells. Mol. Cell. Biol. 21, 1228-1238 (2001).
78. Early, P. et al. Two mRNAs can be produced from a single immunoglobulin μ gene by alternative RNA processing pathways. Cell 20, 313-319 (1980).
79. Rogers, J. et al. Two mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain. Cell 20, 303-312 (1980).
80. Harding, H. P., Calfon, M., Urano, F., Novoa, I. & Ron, D. Transcriptional and translational control in the mammalian unfolded protein response. Annu. Rev. Cell Dev. Biol. 18, 575-599 (2002).
81. Gass, J. N., Gunn, K. E., Sriburi, R. & Brewer, J. W. Stressed-out B cells? Plasma-cell differentiation and the unfolded protein response. Trends Immunol. 25, 17-24 (2004).
82. Gass, J. N., Gifford, N. M. & Brewer, J. W. Activation of an unfolded protein response during differentiation of antibody-secreting B cells. J. Biol. Chem. 277, 49047-49054 (2002).
83. Calfon, M. et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415, 92-96 (2002).
84. Iwakoshi, N. N. et al. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nature Immunol. 4, 321-329 (2003).
85. Yoshida, H. et al. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20, 6755-6767 (2000).
86. van Anken, E. et al. Sequential waves of functionally related proteins are expressed when B cells prepare for antibody secretion. Immunity 18, 243-253 (2003).
87. Vieira, P. & Rajewsky, K. The half-lives of serum immunoglobulins in adult mice. Eur. J. Immunol. 18, 313-316 (1988).
88. Slifka, M. K., Matloubian, M. & Ahmed, R. Bone marrow is a major site of long-term antibody production after acute viral infection. J. Virol. 69, 1895-1902 (1995).
89. Manz, R. A., Thiel, A, & Radbruch, A. Lifetime of plasma cells in the bone marrow. Nature 388, 133-134 (1997).
90. Slifka, M. K., Antia, R., Whitmire, J. K. & Ahmed, R. Humoral immunity due to long-lived plasma cells. Immunity 8, 363-372 (1998). In this study, adoptive transfer of antigen-specific plasma cells to naive mice was used to show that long-lived plasma cells survive and secrete antibody for more than 1 year, and this occurs in the absence of any detectable memory cells.
91. Manz, R. A., Lohning, M., Cassese, G., Thiel, A. & Radbruch, A. Survival of long-lived plasma cells is independent of antigen. Int. Immunol. 10, 1703-1711 (1998).
92. Sze, D. M., Toellner, K. M., Garcia de Vinuesa, C., Taylor, D. R. & MacLennan, I. C. Intrinsic constraint on plasmablast growth and extrinsic limits of plasma cell survival. J. Exp. Med. 192, 813-821 (2000).
93. Knodel, M., Kuss, A. W., Lindemann, D., Berberich, I. & Schimpl, A. Reversal of Blimp-1-mediated apoptosis by A1, a member of the Bcl-2 family. Eur. J. Immunol. 29, 2988-2998 (1999).
94. Arce, S. et al. The role of long-lived plasma cells in autoimmunity. Immunobiology 206, 558-562 (2002).
95. Gorman, C., Leandro, M. & Isenberg, D. B cell depletion in autoimmune disease. Arthritis Res. Ther. 5(Suppl. 4), S17-S21 (2003).
96. Hoyer, B. F. et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J. Exp. Med. 199, 1577-1584 (2004).
97. Takahashi, Y., Dutta, P. R., Cerasoli, D. M. & Kelsoe, G. In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. V. Affinity maturation develops in two stages of clonal selection. J. Exp. Med. 187, 885-895 (1998).
98. Kunkel, E. J. & Butcher, E. C. Plasma-cell homing. Nature Rev. Immunol. 3, 822-829 (2003).
99. Hargreaves, D. C. et al. A coordinated change in chemokine responsiveness guides plasma cell movements. J. Exp. Med. 194, 45-56 (2001).
100. Hopken, U. E., Achtman, A. H., Kruger, K. & Lipp, M. Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and eady immunity against bacterial pathogens. J. Leukoc. Biol. 76, 709-718 (2004).
101. Hauser, A. E. et al. Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response. J. Immunol. 169, 1277-1282 (2002).
102. Odendahl, M. et al. Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood 105, 1614-1621 (2005).
103. Underhill, G. H. et al. IgG plasma cells display a unique spectrum of leukocyte adhesion and homing molecules. Blood 99, 2905-2912 (2002).
104. Manz, R. A. & Radbruch, A. Plasma cells for a lifetime? Eur. J. Immunol. 32, 923-927 (2002).
105. Ellyard, J. I. et al. Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow. Blood 103, 3805-3812 (2004).
106. Minges Wols, H. A., Underhill, G. H., Kansas, G. S. & Witte, P. L. The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity. J. Immunol. 169, 4213-4221 (2002). In this study, isolating normal plasma cells and culturing them in vitro showed that stromal cells provide survival signals to plasma cells. The plasma cells stimulate the stromal cells to produce IL-6, a crucial survival factor.
107. O'Connor, B. R et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J. Exp. Med, 199, 91-98 (2004).
108. Cassese, G. et al. Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J. Immunol. 171, 1684-1690 (2003).
109. Cortes, M. & Georgopoulos, K. Aiolos is required for the generation of high affinity bone marrow plasma cells responsible for long-term immunity. J. Exp. Med. 199, 209-219 (2004). Analysis of mice deficient in Aiolos showed that long-lived plasma cells did not appear in the bone marrow, establishing a requirement for Aiolos in this process.
110. Lee, A. H., Iwakoshi, N. N., Anderson, K. C. & Glimcher, L. H. Proteasome inhibitors disrupt the unfolded protein response in myeloma cells. Proc. Natl Acad. Sci. USA 100, 9946-9951 (2003).
111. Ren, B., Chee, K. J., Kim, T. H. & Maniatis, T. PRDI-BF1/ Blimp-1 repression is mediated by corepressors of the Groucho family of proteins. Genes Dev. 13, 125-137 (1999).
112. Yu, J., Angelin-Duclos, C., Greenwood, J., Liao, J. & Calame, K. Transcriptional repression by Blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase. Mol. Cell. Biol. 20, 2592-2603 (2000).
113. Gyory, I., Wu, J., Fejer, G., Seto, E. & Wright, K. L. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing. Nature Immunol. 5, 299-308 (2004).
114. Lin, K. I., Lin, Y. & Calame, K. Repression of c-myc is necessary but not sufficient for terminal differentiation of B lymphocytes in vitro. Mol. Cell. Biol. 20, 8684-8695 (2000).
115. Berland, R. & Wortis, H. H. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20, 253-300 (2002).
116. Rothstein, T L. Two B-1 or not to be one. J. Immunol. 188, 4257-4261 (2002).
117. Wardemann, H., Boehm, T., Dear, N. & Carsetti, R. B-1a B celils that link the innate and adaptive immune responses are lacking in the absence of the spleen. J. Exp. Med. 195, 771-780 (2002).
118. Bikah, G., Carey, J., Ciallella, J. R., Tarakhovsky, A. & Bondada, S. CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science 274, 1906-1909 (1996).
119. Hippen, K. L., Tze, L. E. & Behrens, T. W. CD5 maintains tolerance in anergic B cells. J. Exp. Med. 191, 883-890 (2000).
120. Berland, R. & Wortis, H. H. Normal B-1a cell development requires B cell-intrinsic NFATc1 activity. Proc. Natl Acad. Sci. USA 100, 13459-13464 (2003).
121. Karras, J. G. et al. Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes. J. Exp. Med. 185, 1035-1042 (1997).
122. Ye, B. H. et al. Alterations of a zinc finger-encoding gene, BCL-6, in diffuse large-cell lymphoma. Science 262, 747-750 (1993).
123. Chang, C. C., Ye, B. H., Chaganti, R. S. & Dalla-Favera, R. BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional represser. Proc. Natl Acad. Sci. USA 93, 6947-6952 (1996).
124. Keller, A. D. & Maniatis, T. Identification and characterization of a novel repressor of β-interferon gene expression. Genes Dev. 5, 868-879 (1991).
125. Kuo, T. C. & Calame, K. L. B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. J. Immunol. 173, 5556-5563 (2004).
126. Marecki, S. & Fenton, M. J. The role of IRF-4 in transcriptional regulation. J. Interferon Cytokine Res. 22, 121-133 (2002).
127. Hemesath, T. J. et al. Microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. Genes Dev. 8, 2770-2780 (1994).
128. Fujita, N. et al. MTA3, a Mi-2/NuRD complex submit, regulates an invasive growth pathway in breast cancer. Cell 113, 207-219 (2003).
129. Adams, B. et al. Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis. Genes Dev. 6, 1589-1607 (1992).
130. Liou, H. C. et al. A new member of the leucine zipper class of proteins that binds to the HLA DR α promoter. Science 247, 1581-1584 (1990).
131. Shapiro-Shelef, M. & Calame, K. Regulation of normal and malignant plasma cells. Curr. Opin. Immunol. 16, 226-230 (2004).
132. Messika, E. et al. Differential effect of Blimp-1 expression on cell fate during B cell development. J. Exp. Med. 188, 515-525 (1998).