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Significance The complexity of the human memory B-lymphocyte compartment is a key component to depict and understand adaptive immunity. Despite numerous prior investigations, the generation of certain memory B-cell subsets, the dependency on T-cell help, and the composition, size, and diversity of clonal expansions are either poorly understood or debated. Here we provide an extensive and tightly controlled immunoglobulin heavy chain variable (IGHV ) gene repertoire analysis of four main human memory B-cell subpopulations, revealing that an ordered diversification in germinal centers determines a highly versatile memory B-cell compartment in humans with surprisingly many very large B-cell clones.

Complexity of the human memory B-cell compartment is determined by the versatility of clonal diversification in germinal centers