Germinal center-associated nuclear protein contributes to affinity maturation of B cell antigen receptor in T cell-dependent responses

Kazuhiko Kuwahara, Satoru Fujimura, Yoshimasa Takahashi, Naomi Nakagata, Toshitada Takemori, Shinichi Aizawa, Nobuo Sakaguchi

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Acquired immunity depends on proliferation and differentiation of antigen (Ag)-specific B cells in germinal centers (GCs) of lymphoid follicles in response to T cell-dependent Ags. Here, we studied the function of GC-associated nuclear protein that is selectively upregulated in GC-B cells. B cell-specific ganp-deficient mice were compromised in affinity maturation of hapten-specific antibodies against T cell-dependent Ags with retarded development of GCs. B cell numbers and development, serum Ig levels, mitogen-induced B cell proliferation in vitro, and responses to T cell-independent Ag were nearly normal; however, the mutant B cells showed a decrease in anti-CD40-induced proliferation and an increased susceptibility to B cell apoptosis in vitro and in vivo. B cell-specific ganp-deficient mice showed a decreased frequency of variable-region somatic mutations, especially of the high-affinity type (W33 → L) in the VH186.2 region against nitrophenyl-chicken gamma globulin, whereas the class switching was normal. We conclude that GC-associated nuclear protein is necessary for generation or maintenance of B cells with high-affinity B cell Ag receptors during the maturation in GCs.

Original languageEnglish
Pages (from-to)1010-1015
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number4
DOIs
Publication statusPublished - 27-01-2004

All Science Journal Classification (ASJC) codes

  • General

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