B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity

Ryohei F. Tsuji, Marian Szczepanik, Ivana Kawikova, Vipin Paliwal, Regis A. Campos, Atsuko Itakura, Moe Akahira-Azuma, Nicole Baumgarth, Leonore A. Herzenberg, Philip W. Askenase

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Contact sensitivity (CS) is a classic example of in vivo T cell immunity in which skin sensitization with reactive hapten leads to immunized T cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T cell recruitment in CS is triggered by local activation of complement, which generates C5a that triggers C5a receptors most likely on mast cells. Here, we show that B-1 cell-derived antihapten IgM antibodies generated within 1 day (d) of immunization combine with local challenge antigen to activate complement to recruit the T cells. These findings overturn three widely accepted immune response paradigms by showing that (a) specific IgM antibodies are required to initiate CS, which is a classical model of T cell immunity thought exclusively due to T cells, (b) CS priming induces production of specific IgM antibodies within 1 d, although primary antibody responses typically begin by day 4, and (c) B-1 cells produce the 1-d IgM response to CS priming, although these cells generally are thought to be nonresponsive to antigenic stimulation. Coupled with previous evidence, our findings indicate that the elicitation of CS is initiated by rapidly formed IgM antibodies. The IgM and challenge antigen likely form local complexes that activate complement, generating C5a, leading to local vascular activation to recruit the antigen-primed effector T cells that mediate the CS response.

Original languageEnglish (US)
Pages (from-to)1277-1290
Number of pages14
JournalJournal of Experimental Medicine
Volume196
Issue number10
DOIs
StatePublished - Nov 18 2002

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Keywords

  • Complement C5 and C5a
  • IgM response
  • Skin immunity
  • T and B cell interactions
  • T cell recruitment

ASJC Scopus subject areas

  • Immunology

Cite this

Tsuji, R. F., Szczepanik, M., Kawikova, I., Paliwal, V., Campos, R. A., Itakura, A., Akahira-Azuma, M., Baumgarth, N., Herzenberg, L. A., & Askenase, P. W. (2002). B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity. Journal of Experimental Medicine, 196(10), 1277-1290. https://doi.org/10.1084/jem.20020649