Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production

Journal of Experimental Medicine

Volumn 203, Issue 6, 2006, Pages 1567-1578

  Ippolito, Gregory C ^a   Schelonka, Robert L ^a   Zemlin, Michael ^a   Ivanov, Ivaylo I ^a   Kobayashi, Ryoki ^a   Zemlin, Cosima ^a   Gartland, G Larry ^a   Nitschke, Lars ^b   Pelkonen, Jukka ^c   Fujihashi, Kohtaro ^a   Rajewsky, Klaus ^d   Schroeder Jr , Harry W ^a  

^a UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^c UNIVERSITY OF EASTERN FINLAND   (Finland)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ARGININE; ASPARAGINE; GLYCINE; HISTIDINE; IMMUNOGLOBULIN; IMMUNOGLOBULIN HEAVY CHAIN; TYROSINE;

ANIMAL CELL; ANTIBODY COMBINING SITE; ANTIBODY PRODUCTION; ANTIBODY TITER; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BONE MARROW; CELL COUNT; CELL FUNCTION; CELL MATURATION; COMPLEMENTARITY DETERMINING REGION; CONTROLLED STUDY; GENE LOCUS; GENE MUTATION; GENE SEQUENCE; HUMORAL IMMUNITY; HYDROPHOBICITY; IMMUNOGLOBULIN BLOOD LEVEL; MOUSE; NONHUMAN; PERITONEAL CAVITY; PRIORITY JOURNAL; PROTEIN CONTENT; SPLEEN;

AMINO ACID SEQUENCE; AMINO ACIDS; ANIMALS; ANTIBODY FORMATION; B-LYMPHOCYTES; IMMUNOGLOBULIN HEAVY CHAINS; MICE; MICE, INBRED BALB C; MOLECULAR SEQUENCE DATA;

EID: 33745053586     PISSN: 00221007     EISSN: 00221007     Source Type: Journal    
DOI: 10.1084/jem.20052217     Document Type: Article

References (49)

1. Tonegawa, S. 1983. Somatic generation of antibody diversity. Nature. 302:575-581.
2. Alt, F.W., and D. Baltimore. 1982. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-J heavy fusions. Proc. Natl. Acad. Sci. USA. 79:4118-4122.
3. Rajewsky, K. 1996. Clonal selection and learning in the antibody system. Nature. 381:751-758.
4. Kabat, E.A., T.T. Wu, H.M. Perry, K.S. Gottesman, and C. Foeller. 1991. Sequences of proteins of immunological interest. U.S.Department of Health and Human Services, Bethesda, Maryland. 2387 pp.
5. Padlan, E.A. 1994. Anatomy of the antibody molecule. Mol. Immunol. 31:169-217.
6. Xu, J.L., and M.M. Davis. 2000. Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity. 13:37-45.
7. Ichihara, Y., H. Hayashida, S. Miyazawa, and Y. Kurosawa. 1989. Only DFL16, DSP2, and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. Eur. J. Immunol. 19:1849-1854.
8. Ivanov, I.I., J.M. Link, G.C. Ippolito, and H.W. Schroeder Jr. 2002. Constraints on hydropathicity and sequence composition of HCDR3 are conserved across evolution. In The Antibodies. M. Zanetti and J.D. Capra, editors. Taylor and Francis Group, London. 43-67.
9. Gu, H., I. Forster, and K. Rajewsky. 1990. Sequence homologies, N sequence insertion and JH gene utilization in VH-D-JH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 9:2133-2140.
10. Feeney, A.J., S.H. Clarke, and D.E. Mosier. 1988. Specific H chain junctional diversity may be required for non-T15 antibodies to bind phosphorylcholine. J. Immunol. 141:1267-1272.
11. Kurosawa, Y., and S. Tonegawa. 1982. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J. Exp. Med. 155:201-218.
12. Schelonka, R.L., I.I. Ivanov, D. Jung, G.C. Ippolito, L. Nitschke, Y. Zhuang, G.L. Gartland, J. Pelkonen, F.W. Alt, K. Rajewsky, and H.W. Schroeder Jr. 2005. A single DH gene segment is sufficient for B cell development and immune function. J. Immunol. 175:6624-6632.
13. Hardy, R.R., and K. Hayakawa. 2001. B cell development pathways. Annu. Rev. Immunol. 19:595-621.
14. Ivanov, I.I., R.L. Schelonka, Y. Zhuang, G.L. Gartland, M. Zemlin, and H.W. Schroeder Jr. 2005. Development of the expressed immunoglobulin CDR-H3 repertoire is marked by focusing of constraints in length, amino acid utilization, and charge that are first established in early B cell progenitors. J. Immunol. 174:7773-7780.
15. Blomberg, B., W.R. Geckeler, and M. Weigert. 1972. Genetics of the antibody response to dextran in mice. Science. 177:178-180.
16. Stohrer, R., and J.F. Kearney. 1983. Fine idiotype analysis of B cell precursors in the T-dependent and T-independent responses to α1-3 dextran in BALB/c mice. J. Exp. Med. 158:2081-2094.
17. Imanishi-Kari, T., E. Rajnavolgyi, T. Takemori, R.S. Jack, and K. Rajewsky. 1979. The effect of light chain gene expression on the inheritance of an idiotype associated with primary anti-(4-hydroxy-3-nitrophenyl)acetyl(NP) antibodies. Eur. J. Immunol. 9:324-331.
18. Volk, W.A., B. Bizzini, R.M. Snyder, E. Bernhard, and R.R. Wagner. 1984. Neutralization of tetanus toxin by distinct monoclonal antibodies binding to multiple epitopes on the toxin molecule. Infect. Immun. 45:604-609.
19. VanCott, J.L., H.F. Staats, D.W. Pascual, M. Roberts, S.N. Chatfield, M. Yamamoto, M. Coste, P.B. Carter, H. Kiyono, and J.R. McGhee. 1996. Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella. J. Immunol. 156:1504-1514.
20. Williams, G.S., A. Martinez, A. Montalbano, A. Tang, A. Mauhar, K.M. Ogwaro, D. Merz, C. Chevillard, R. Riblet, and A.J. Feeney. 2001. Unequal VH gene rearrangement frequency within the large VH7183 gene family is not due to recombination signal sequence variation, and mapping of the genes shows a bias of rearrangement based on chromosomal location. J. Immunol. 167:257-263.
21. Huetz, F., L. Carlsson, U.-C. Tornberg, and D. Holmberg. 1993. V-region directed selection in differentiating B lymphocytes. EMBO J. 12:1819-1826.
22. Marshall, A.J., G.E. Wu, and G.J. Paige. 1996. Frequency of VH81x usage during B cell development: initial decline in usage is independent of Ig heavy chain cell surface expression. J. Immunol. 156:2077-2084.
23. Viale, A.C., A. Coutinho, and A.A. Freitas. 1992. Differential expression of VH gene families in peripheral B cell repertoires of newborn or adult immunoglobulin H chain congenic mice. J. Exp. Med. 175:1449-1456.
24. Kirkham, P.M., and H.W. Schroeder Jr. 1994. Antibody structure and the evolution of immunoglobulin V gene segments. Semin. Immunol. 6:347-360.
25. Chen, L., S. Chang, and C. Mohan. 2002. Molecular signatures of antinuclear antibodies-contributions of heavy chain CDR residues. Mol. Immunol. 39:333-347.
26. Nitschke, L., J. Kestler, T. Tallone, S. Pelkonen, and J. Pelkonen. 2001. Deletion of the DQ52 element within the Ig heavy chain locus leads to a selective reduction in VDJ recombination and altered D gene usage. J. Immunol. 166:2540-2552.
27. H rearrangement violating the 12/23 rule. J. Exp. Med. 201:341-348.
28. Rolink, A.G., C. Schaniel, J. Andersson, and F. Melchers. 2001. Selection events operating at various stages in B cell development. Curr. Opin. Immunol. 13:202-207.
29. Nemazee, D., and M. Weigert. 2000. Revising B cell receptors. J. Exp. Med. 191:1813-1817.
30. Forster, I., P. Vieira, and K. Rajewsky. 1989. Flow cytometric analysis of cell proliferation dynamics in the B cell compartment of the mouse. Int. Immunol. 1:321-331.
31. Levine, M.H., A.M. Haberman, D.B. Sant'Angelo, L.G. Hannum, M.P. Cancro, C.A. Janeway Jr., and M.J. Shlomchik. 2000. A B-cell receptor-specific selection step governs immature to mature B cell differentiation. Proc. Natl. Acad. Sci. USA. 97:2743-2748.
32. Mandik-Nayak, L., A. Bui, H. Noorchashm, A. Eaton, and J. Erikson. 1997. Regulation of anti-double-stranded DNA B cells in nonautoimmune mice: localization to the T-B interface of the splenic follicle. J. Exp. Med. 186:1257-1267.
33. Lopes-Carvalho, T., and J.F. Kearney. 2004. Development and selection of marginal zone B cells. Immunol. Rev. 197:192-205.
34. Gu, H., D. Tarlinton, W. Muller, K. Rajewsky, and I. Forster. 1991. Most peripheral B cells in mice are ligand selected. J. Exp. Med. 173:1357-1371.
35. Li, Y., H. Li, and M. Weigert. 2002. Autoreactive B cells in the marginal zone that express dual receptors. J. Exp. Med. 195:181-188.
36. Shlomchik, M., M. Mascelli, H. Shan, M.Z. Radic, D. Pisetsky, A. Marshak-Rothstein, and M. Weigert. 1990. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J. Exp. Med. 171:265-297.
37. Wardemann, H., S. Yurasov, A. Schaefer, J.W. Young, E. Meffre, and M.C. Nussenzweig. 2003. Predominant autoantibody production by early human B cell precursors. Science. 301:1374-1377.
38. Zemlin, M., M. Klinger, J. Link, C. Zemlin, K. Bauer, J.A. Engler, H.W. Schroeder Jr., and P.M. Kirkham. 2003. Expressed murine and human CDR-H3 intervals of equal length exhibit distinct repertoires that differ in their amino acid composition and predicted range of structures. J. Mol. Biol. 334:733-749.
39. Raaphorst, F.M., C.S. Raman, B.T. Nall, and J.M. Teale. 1997. Molecular mechanisms governing reading frame choice of immunoglobulin diversity genes. Immunol. Today. 18:37-43.
40. Schroeder, H.W., Jr., G.C. Ippolito, and S. Shiokawa. 1998. Regulation of the antibody repertoire through control of HCDR3 diversity. Vaccine. 16:1383-1390.
41. Coutinho, A. 2001. Gigas and anthropiscus: evolution and development of Cohen's immunological homunculus. In Autoimmunity and Emerging Diseases. L. Steinman, editor. The Center for the Study of Emerging Diseases, Jerusalem. 54-63.
42. Boersch-Supan, M.E., S. Agarwal, M.E. White-Scharf, and T. Imanishi-Kari. 1985. Heavy chain variable region. Multiple gene segments encode anti-4-(hydroxy-3-nitro-phenyl)acetyl idiotypic antibodies. J. Exp. Med. 161:1272-1292.
43. + T cells in nasopharyngeal-associated lymphoreticular tissue. J. Immunol. 170:1754-1762.
44. Torres, R., and R. Kuhn. 1997. Laboratory Protocols for Conditional Gene Targeting. Oxford University Press, Oxford. 184 pp.
45. Reth, M., G.J. Hammerling, and K. Rajewsky. 1978. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur. J. Immunol. 8:393-400.
46. Allman, D., R.C. Lindsley, W. DeMuth, K. Rudd, S.A. Shinton, and R.R. Hardy. 2001. Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation. J. Immunol. 167:6834-6840.
47. Oliver, A.M., F. Martin, G.L. Gartland, R.H. Carter, and J.F. Kearney. 1997. Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. Eur. J. Immunol. 27:2366-2374.
48. Loder, F., B. Mutschler, R.J. Ray, C.J. Paige, P. Sideras, R. Torres, M.C. Lamers, and R. Carsetti. 1999. B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J. Exp. Med. 190:75-89.
49. Eisenberg, D. 1984. Three-dimensional structure of membrane and surface proteins. Annu. Rev. Biochem. 53:595-623.