alexa Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease.
Immunology

Immunology

Journal of Clinical & Cellular Immunology

Author(s): Ma CS, Pittaluga S, Avery DT, Hare NJ, Maric I,

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Abstract Individuals with X-linked lymphoproliferative disease (XLP) display defects in B cell differentiation in vivo. Specifically, XLP patients do not generate a normal number of CD27 memory B cells, and those few that are present are IgM. Recent studies have suggested that IgMCD27 B cells are not true memory cells, but rather B cells that guard against T cell-independent pathogens. Here we show that human XLP IgMCD27 B cells resemble normal memory B cells both morphologically and phenotypically. Additionally, IgMCD27 B cells exhibited functional characteristics of normal memory B cells, including the ability to secrete more Ig than naive B cells in response to both T cell-dependent and -independent stimuli. Analysis of spleens from XLP patients revealed a paucity of germinal centers (GCs), and the rare GCs detected were poorly formed. Despite this, Ig variable region genes expressed by XLP IgMCD27 B cells had undergone somatic hypermutation to an extent comparable to that of normal memory B cells. These findings reveal a differential requirement for the generation of IgM and Ig isotype-switched memory B cells, with the latter only being generated by fully formed GCs. Production of affinity-matured IgM by IgMCD27 B cells may protect against pathogens to which a normal immune response is elicited in XLP patients.
This article was published in J Clin Invest and referenced in Journal of Clinical & Cellular Immunology

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