Receptor revision plays no major role in shaping the receptor repertoire of human memory B cells after the onset of somatic hypermutation

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Abstract
In order to determine whether V gene replacement accompanies somatic hypermutation in the germinal center (GC) reaction in the human, we analyzed VκJκ and VIJλ joints and the kappa-deleting element in single λ+ naive and post GC B cells for rearrangements at the κ and λ loci. Among 265 λ+ post GC B cells, not a single unequivocal and only two potential examples of a cell that switched to λ light chain expression after accumulation of (unfavorable) mutations in its productive Vκ rearrangement were observed. Taking the PCR efficiency into account, the frequency of such cells is likely below 3 %. In addition, heavy and light chain gene rearrangements were amplified and sequenced from the oligoclonal population of IgD-only peripheral blood post GC B cells which display extensive intraclonal sequence diversity. Among 61 IgD-only B cells belonging to 15 clones with intraclonal diversity, no combination of V gene rearrangements indicating receptor revision during clonal expansion was observed. Moreover, among 124 and 49 VH genes amplified from IgD-onlyand class-switched B cells, respectively, not a single example of VH revision through VH hybrid generation was detected. These results suggest that in the human GC reaction V gene replacement either does not usually accompany somatic hypermutation or is mostly counterselected.