Distinction of the memory B cell response to cognate antigen versus bystander inflammatory signals.

Full Abstract

The hypothesis that bystander inflammatory signals promote memory B cell (B(MEM)) self-renewal and differentiation in an antigen-independent manner is critically evaluated herein. To comprehensively address this hypothesis, a detailed analysis is presented examining the response profiles of B-2 lineage B220(+)IgG(+) B(MEM) toward cognate protein antigen in comparison to bystander inflammatory signals. After in vivo antigen encounter, quiescent B(MEM) clonally expand. Surprisingly, proliferating B(MEM) do not acquire germinal center (GC) B cell markers before generating daughter B(MEM) and differentiating into plasma cells or form structurally identifiable GCs. In striking contrast to cognate antigen, inflammatory stimuli, including Toll-like receptor agonists or bystander T cell activation, fail to induce even low levels of B(MEM) proliferation or differentiation in vivo. Under the extreme conditions of adjuvanted protein vaccination or acute viral infection, no detectable bystander proliferation or differentiation of B(MEM) occurred. The absence of a B(MEM) response to nonspecific inflammatory signals clearly shows that B(MEM) proliferation and differentiation is a process tightly controlled by the availability of cognate antigen.

Author information

Author/s: Benson, Micah J (MJ); Elgueta, Raul (R); Schpero, William (W); Molloy, Michael (M); Zhang, Weijun (W); Usherwood, Edward (E); Noelle, Randolph J (RJ);

Affiliation: Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03756, USA. Benson(-atsign-)IDI.Harvard.edu

Grants: R01A1026296 (Agency:PHS HHS) ; R01A108896 (Agency:PHS HHS) ; T32AI07363 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of experimental medicine (J Exp Med), published in United States. (Language: eng)

Reference: 2009-Aug; vol 206 (issue 9) : pp 2013-25

Dates: Created 2009/09/01; Completed 2009/10/05;

PMID: 19703988, status: MEDLINE (last retrieved date: 10/5/2009)

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