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 VH genes and show preferential Igλ usage. To further characterize these peculiar cells and gain insight into their generation, we analysed rearranged VH and VL genes of single IgD-only λ+ 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 VH genes but also present in VL 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 VH3-30 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 Cδ and often λ light chains and the VH3-30 segment, and are selected for deletion of Cμ. IgD-only B cells may hence represent a unique B lineage subset generated in response to particular antigens.