B cell-dependent T cell responses: IgM antibodies are required to elicit contact sensitivity. J Exp Med 2002 Nov 18;196(10):1277-90
Date
11/20/2002Pubmed ID
12438420Pubmed Central ID
PMC2193992DOI
10.1084/jem.20020649Scopus ID
2-s2.0-0037131979 (requires institutional sign-in at Scopus site) 117 CitationsAbstract
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.
Author List
Tsuji RF, Szczepanik M, Kawikova I, Paliwal V, Campos RA, Itakura A, Akahira-Azuma M, Baumgarth N, Herzenberg LA, Askenase PWAuthor
Vipin Paliwal PhD Associate Professor in the Physics & Chemistry department at Milwaukee School of EngineeringMESH terms used to index this publication - Major topics in bold
AnimalsAutoantibodies
B-Lymphocytes
Cell Separation
Complement C5
Dermatitis, Contact
Flow Cytometry
Immunoglobulin M
Male
Mice
Mice, Inbred CBA
T-Lymphocytes
