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J. Exp. Med.,
Volume 188, Number 8, October 19, 1998 1453-1464
By
From the * Department of Pediatrics and the The B cell receptor (BCR) triggers a variety of biological responses that differ depending upon
the properties of the antigen. A panel of M13 phage-displayed peptide ligands with varying affinity for the 3-83 antibody was generated to explore the role of antigen-BCR affinity in cell
activation studies using primary 3-83 transgenic mouse B cells. Multiple parameters of activation were measured. T cell-independent B cell proliferation, antibody secretion, induction of
germline immunoglobulin Department of Medicine, National Jewish Medical and
Research Center, Denver, Colorado 80206; the § Department of Immunology, University of Colorado
Health Science Center, Denver, Colorado 80220; EISAI London Research Laboratories, University
College of London, London WC1E 6BT; the ¶ Department of Biology, University of North Carolina
at Chapel Hill, Chapel Hill, North Carolina 27599; and the ** Department of Pharmacology,
University of Wisconsin, Madison, Wisconsin 53706
1 transcripts, and B cell production of interleukin (IL) 2 and interferon responses were better correlated with antigen-BCR affinity than with receptor occupancy. In contrast, other responses, such as upregulation of major histocompatibility complex
class II and B7.2 (CD86), secretion of IL-6, and B cell proliferation in the context of CD40
signaling were only weakly dependent on antigen affinity. Biochemical analysis revealed that at
saturating ligand concentrations the ability of phage to stimulate some early signaling responses,
such as Ca++ mobilization and tyrosine phosphorylation of syk or Ig
, was highly affinity dependent, whereas the ability to stimulate Lyn phosphorylation was less so. These data suggest
that the BCR is capable of differential signaling. The possibility that differential BCR signaling
by antigen determines whether an antibody response will be T independent or dependent is
discussed.
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