Intrinsic (genetic) and extrinsic (antigen and microenvironment) factors drive B cell heterogeneity.  Early studies of B cell diversity focused upon the characterization of X-chromosome-linked immune- defective (XID) mice.  The failure of a subset of B cells to mature was found to be due to an intrinsic signaling defect in mice expressing xid.  Subsequent research led to the description of B-1 cells, a subpopulation of B cells noted for enhanced representation in the peritoneal cavity and expression of self-reactive immunoglobulin genes.  The interplay of genes and environment drive the development of this unique B cell subset.  Further evidence that nature and nurture influence B cell heterogeneity is found with the B cells of the splenic marginal zone. Positioned to filter particulate antigens from the blood, this subset expresses unique specificities selected by commensal flora and self-antigens.  Thus, mature B cells are heterogeneous in their anatomical distribution based upon specific microenvironments and their associated antigens selecting for particular immunoglobulin specificities.  The contribution of apoptotic products and neighboring phagocytes in creating distinctive microenvironments that diversify the mammalian B cell pool is discussed.