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

35 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

Fingerprint

TNF Receptor-Associated Factor 6
T-cells
Humoral Immunity
humoral immunity
B-lymphocytes
B-Lymphocytes
T-lymphocytes
Cells
T-Lymphocytes
antigens
Immunoglobulin M
Antigens
T Independent Antigens
Immunoglobulin Class Switching
B-Lymphoid Precursor Cells
Tumor Necrosis Factor Receptors
Toll-Like Receptors
Gene Deletion
receptors
Plasma Cells

ASJC Scopus subject areas

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

Cite this

Kobayashi, T., Kim, T. S., Jacob, A., Walsh, M. C., Kadono, Y., Fuentes-Pananá, E., ... 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

TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and-independent humoral immune responses. / Kobayashi, Takashi; Kim, Tae Soo; Jacob, Anand; Walsh, Matthew C.; Kadono, Yuho; Fuentes-Pananá, Ezequiel; Yoshioka, Tomoko; Yoshimura, Akihiko; Yamamoto, Masahiro; Kaisho, Tsuneyasu; Akira, Shizuo; Monroe, John G.; Choi, Yongwon.

In: PLoS One, Vol. 4, No. 3, e4736, 09.03.2009.

Research output: Contribution to journalArticle

Kobayashi, T, Kim, TS, Jacob, A, Walsh, MC, Kadono, Y, Fuentes-Pananá, E, Yoshioka, T, Yoshimura, A, Yamamoto, M, Kaisho, T, Akira, S, Monroe, JG & 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, vol. 4, no. 3, e4736. https://doi.org/10.1371/journal.pone.0004736
Kobayashi, Takashi ; Kim, Tae Soo ; Jacob, Anand ; Walsh, Matthew C. ; Kadono, Yuho ; Fuentes-Pananá, Ezequiel ; Yoshioka, Tomoko ; Yoshimura, Akihiko ; Yamamoto, Masahiro ; Kaisho, Tsuneyasu ; Akira, Shizuo ; Monroe, John G. ; Choi, Yongwon. / TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and-independent humoral immune responses. In: PLoS One. 2009 ; Vol. 4, No. 3.
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