In humans and mice, bone marrow is the site of B-cell origin and development. Arising from lymphoid progenitors, immature B cells proliferate and differentiate within the bone marrow, and stromal cells within the bone marrow interact directly with the B cells and secrete various cytokines that are required for development. Like thymic selection during T-cell maturation, a selection process within the bone marrow eliminates B cells with self-reactive antibody receptors. Bone marrow is not the site of B-cell development in all species. In birds, a lymphoid organ called the bursa of Fabricius, a lymphoid tissue associated with the gut, is the primary site of B-cell maturation. In mammals such as primates and rodents, there is no bursa and no single counterpart to it as a primary lymphoid organ. In cattle and sheep, the primary lymphoid tissue hosting the maturation, proliferation, and diversification of B cells early in gestation is the fetal spleen. Later in gestation, this function is assumed by a patch of tissue embedded in the wall of the intestine called the ileal Peyer’s patch,which contains a large number (>1010) B cells. The rabbit, too, uses gut-associated tissues such as the appendix as primary lymphoid tissue for important steps in the proliferation and diversification of B cells.