TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and -Independent Humoral Immune Responses

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:
  • PLoS ONE

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2009