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Identification of semaphorin 4B as a negative regulator of basophil-mediated immune responses.

Basophils are strong mediators of Th2 responses during helminthic infections. Recently, basophils were shown to function as APCs and promote both Th2 skewing and humoral memory responses. However, the mechanisms that regulate basophils are still unclear. In this article, we show that a class IV semaphorin, Sema4B, negatively regulates basophil functions through T cell-basophil contacts. In a screen to identify semaphorins that function in the immune system, we determined that Sema4B is expressed in T and B cells. Interestingly, Sema4B(-/-) mice had considerably increased serum IgE levels despite normal lymphocyte and dendritic cell functions. Recombinant Sema4B significantly inhibited IL-4 and IL-6 production from basophils in response to various stimuli, including IL-3, papain, and FcεRI cross-linking. In addition, T cell-derived Sema4B, which accumulated at contact sites between basophils and CD4(+) T cells, suppressed basophil-mediated Th2 skewing, suggesting that Sema4B regulates basophil responses through cognate cell-cell contacts. Furthermore, Sema4B(-/-) mice had enhanced basophil-mediated memory IgE production, which was abolished by treating with an anti-FcεRIα Ab. Collectively, these results indicate that Sema4B negatively regulates basophil-mediated Th2 and humoral memory responses.

Pubmed ID: 21270411


  • Nakagawa Y
  • Takamatsu H
  • Okuno T
  • Kang S
  • Nojima S
  • Kimura T
  • Kataoka TR
  • Ikawa M
  • Toyofuku T
  • Katayama I
  • Kumanogoh A


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

March 1, 2011

Associated Grants


Mesh Terms

  • Animals
  • B-Lymphocytes
  • Basophils
  • Cytokines
  • Down-Regulation
  • Gene Expression Regulation
  • Immune Tolerance
  • Immunoglobulin E
  • Immunologic Memory
  • Interleukin-4
  • Interleukin-6
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, Transgenic
  • Semaphorins
  • T-Lymphocytes
  • Th2 Cells