A model for the development of human IgD-only B cells: Genotypic analyses suggest their generation in superantigen driven immune responses.

Human peripheral blood (PB) B cells expressing only IgD and tonsillar IgD-secreting plasma cells carry highly mutated V(H) genes and show preferential Iglambda usage. To further characterize these peculiar cells and gain insight into their generation, we analysed rearranged V(H) and V(L) genes of single IgD-only lambda(+) PB B cells and IgD(+) plasma cells from four individuals each. We demonstrate that the high somatic hypermutation activity in these cells is not restricted to V(H) genes but also present in V(L) genes. Moreover, not only PB IgD-only B cells, as reported earlier, but also IgD-expressing plasma cells often belong to very large clones. Surprisingly, the V(H)3-30 gene segment was used in each PB donor by >30% of IgD-only cells and in 2 tonsils by >50% of IgD plasma cells, whereas it was used less frequent in other B cells. All these features fit to a model in which IgD-only cells develop in superantigen-driven germinal center reactions, in which B cells are activated by binding of antigens to constant parts of Cdelta and often lambda light chains and the V(H)3-30 segment, and are selected for deletion of Cmu. IgD-only B cells may hence represent a unique B lineage subset generated in response to particular antigens.