Successful antibody production in vivo depends on a number of cellular events, one of the most important of these being cognate B cell-T cell interaction. To examine this phenomenon in vitro, homogeneous populations of hen egg lysozyme (HEL)-specific small resting B cells and naive CD4+ HEL-specific T cells (derived from immunoglobulin [Ig] and T cell receptor transgenic mice, respectively) were cultured together. On addition of intact HEL protein. HEL-specific B cells increase their expression of activation molecules, including a B7-related protein and CD44, and enlarge into blast cells. Within the same cultures, HEL-specific CD4+ T cells also increase expression of the activation markers CD69 and CD44, enlarge, secrete lymphokines, and proliferate. This response is radiation sensitive, supporting the conclusion that HEL-specific B cells present antigen to and activate the naive T cells. By contrast, when a synthetic peptide fragment of HEL is used to bypass B cell antigen-receptor engagement, the naive T cells enlarge and display activation antigens, but fail to produce lymphokines, proliferate, or promote B cell blastogenesis. Presentation of HEL by tolerant B cells, which are no longer able to signal effectively through their antigen receptors, results in an identical pattern of incomplete T cell activation. Addition of a stimulating anti-CD28 antibody and blocking of CD28 signals with CTLA4/Ig fusion protein both show that complete activation of naive CD4+ T cells depends on the initial induction of B7 and related costimulatory molecules after HEL binding to nontolerant HEL-specific B cells. Thus, in the absence of adequate constimulation from the B cell, naive CD4+ T cells undergo a form of "partial activation" in which they upregulate surface expression of certain T cell activation antigens, but fail to efficiently produce lymphokine and proliferate. This may explain the different conclusions that have been reached regarding the consequences of B cell antigen presentation to T cells, in that the ability of B cells to activate naive CD4+ T cells depends both on their specificity and their activation state.
Article|
May 01 1994
Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells.
W Y Ho,
W Y Ho
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
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M P Cooke,
M P Cooke
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
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C C Goodnow,
C C Goodnow
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
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M M Davis
M M Davis
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
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W Y Ho
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
M P Cooke
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
C C Goodnow
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
M M Davis
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (5): 1539–1549.
Citation
W Y Ho, M P Cooke, C C Goodnow, M M Davis; Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells.. J Exp Med 1 May 1994; 179 (5): 1539–1549. doi: https://doi.org/10.1084/jem.179.5.1539
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