The avian B-cell receptor complex: distinct roles of Igalpha and Igbeta in B-cell development

The bursa of Fabricius has evolved in birds as a gut-associated site of B-cell lymphopoiesis that is segregated from the development of other hematopoietic lineages. Despite differences in the developmental progression of chicken as compared to murine B-cell lymphopoiesis, cell-surface immunoglobulin (sIg) expression has been conserved in birds as an essential checkpoint in B-cell development. B-cell precursors that express an sIg complex that includes the evolutionarily conserved Igalpha/beta heterodimer colonize lymphoid follicles in the bursa, whereas B-cell precursors that fail to express sIg due to non-productive V(D)J recombination are eliminated. Productive retroviral gene transfer has allowed us to introduce chimeric receptor constructs into developing B-cell precursors in vivo. Chimeric proteins comprising the extracellular and transmembrane regions of murine CD8alpha fused to the cytoplasmic domain of chicken Igalpha efficiently supported B-cell development in precursors that lacked endogenous sIg expression. By contrast, expression of an equivalent chimeric receptor containing the cytoplasmic domain of Igbeta actively inhibited B-cell development. Consequently, the cytoplasmic domains of Igalpha and Igbeta play functionally distinct roles in chicken B-cell development.