TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and-independent humoral immune responses

Takashi Kobayashi, Tae Soo Kim, Anand Jacob, Matthew C. Walsh, Yuho Kadono, Ezequiel Fuentes-Pananá, Tomoko Yoshioka, Akihiko Yoshimura, Masahiro Yamamoto, Tsuneyasu Kaisho, Shizuo Akira, John G. Monroe, Yongwon Choi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

TNF receptor superfamily members, such as CD40 and the Toll-like receptors (TLRs), regulate many aspects of B cell differentiation and activation. TRAF6 is an intracellular signaling adaptor molecule for these receptors, but its role in B cells has not been clarified by previous genetic approaches, as the systemic deletion of the TRAF6 gene results in perinatal lethality. Here we show that B cell-specific TRAF6 deficiency results in a reduced number of mature B cells in the bone marrow and spleen. Optimal T cell-dependent (TD) antigen responses, as characterized by isotype switching and long-lived plasma cell generation, are also impaired in B cell-specific TRAF6-deficient mice. B cell-specific TRAF6-deficient mice also exhibit lower levels of serum IgM and IgG2b and defective antigen-specific IgM production in response to T cell-independent (TI) antigens. Unexpectedly, TRAF6-deficient B cell progenitors are unable to generate CD5+ B-1 cells. These results reveal critical roles for TRAF6 in TD and TI humoral immune responses and in inductive fate decisions necessary to generate the B-1 B cell compartment.

Original languageEnglish
Article numbere4736
JournalPloS one
Volume4
Issue number3
DOIs
Publication statusPublished - 2009 Mar 9

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kobayashi, T., Kim, T. S., Jacob, A., Walsh, M. C., Kadono, Y., Fuentes-Pananá, E., Yoshioka, T., Yoshimura, A., Yamamoto, M., Kaisho, T., Akira, S., Monroe, J. G., & Choi, Y. (2009). TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and-independent humoral immune responses. PloS one, 4(3), [e4736]. https://doi.org/10.1371/journal.pone.0004736