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Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells.

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.

Pubmed ID: 7909325


  • Ho WY
  • Cooke MP
  • Goodnow CC
  • Davis MM


The Journal of experimental medicine

Publication Data

May 1, 1994

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 2T32GM07365
  • Agency: NIAID NIH HHS, Id: AI-19512

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD28
  • B-Lymphocytes
  • CD4-Positive T-Lymphocytes
  • Clonal Anergy
  • Female
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Restriction Mapping