Human IgM-expressing memory B cells

Bettina Budeus

doi:10.3389/fimmu.2023.1308378

Human IgM-expressing memory B cells

2023-12-08

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DOI：10.3389/fimmu.2023.1308378

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A hallmark of T cell dependent (TD) humoral immune responses is the generation of long-lived memory B cells. The generation of these cells occurs primarily in the germinal center (GC) reaction, where antigen-activated B cells undergo affinity maturation as a major consequence of the combined processes of proliferation, somatic hypermutation of their immunoglobulin V (IgV) region genes, and selection for improved affinity of their B-cell antigen receptors. As many B cells also undergo class-switching to IgG or IgA in these TD responses, there was traditionally a focus on class-switched memory B cells in both murine and human studies on memory B cells. However, it has become clear that there is also a large subset of IgM-expressing memory B cells, which have important phenotypic and functional similarities but also differences to class-switched memory B cells. There is an ongoing discussion about the origin of distinct subsets of human IgM+ B cells with somatically mutated IgV genes. We argue here that the vast majority of human IgM-expressing B cells with somatically mutated IgV genes in adults is indeed derived from GC reactions, even though a generation of some mostly lowly mutated IgM+ B cells from other differentiation pathways, mainly in early life, may exist.

Keywords:

B cells

CD27

class switch recombination

germinal center

IgD

immunoglobulin V genes

marginal zone

somatic hypermutation

Human IgM-expressing memory B cells

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