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Detection and Enrichment of Rare Antigen-specific B Cells for Analysis of Phenotype and Function
09:25

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Published on: February 16, 2017

B cell receptor affinity and B cell subset identity integrate to define the effectiveness, affinity threshold, and

Ramiro Diz1, Suzanne K McCray, Stephen H Clarke

  • 1Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|September 5, 2008
PubMed

In this study we show that BCR affinity and subset identity make unique contributions to anergy. Analysis of anti-Smith (Sm) B cells of different affinities indicates that increasing affinity improves anergy's effectiveness while paradoxically increasing the likelihood of marginal zone (MZ) and B-1 B cell differentiation rather than just follicular (FO) B cell differentiation. Subset identity in turn determines the affinity threshold and mechanism of anergy. Subset-specific affinity thresholds for anergy induction allow discordant regulation of low-affinity anti-Sm FO and MZ B cells and could account for the higher frequency of autoreactive MZ B cells than that of FO B cells in normal mice. The mechanism of anergy changes during differentiation and differs between subsets. This is strikingly illustrated by the observation that blockade of BCR-mediated activation of FO and MZ B cells occurs at different levels in the signaling cascade. Thus, attributes unique to B cells of each subset integrate with signals from the BCR to determine the effectiveness, affinity threshold, and mechanism of anergy.

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