Phenotypic and genetic characterization of a unique B lymphocyte deficiency in strain A/WySnJ mice

The elucidation of B lymphocyte development has been partially achieved through genetic models such as the X-linked immunodeficiency (xid) mutation. We discovered a unique B lymphocyte developmental defect in strain A/WySnJ mice. We used single- and two-color flow cytometry to analyze lymphocytes from A/J and A/WySnJ mice. Adult A/WySnJ mice had a severe B cell deficiency, which was apparent in the spleen, lymph nodes, peritoneum and peripheral blood, compared to adult A/J mice. An ontogeny study revealed that a developmental defect, inhibiting B lymphocyte maturation or differentiation but not B lymphopoiesis, was responsible for the deficiency. This maturational defect blocked the production of B220hi/Iahi/surface IgMlo B cells, and was manifested in the adult bone marrow and neonatal spleen, but not the adult spleen. Neither Ly-1 B cells nor peripheral T cells were apparently affected by the A/WySnJ defect. The B cell immunodeficiency segregated as an autosomal co-dominant trait in F1 and F2 mice. We propose that A/WySnJ mice have a novel genetic defect arresting B cell differentiation in adult bone marrow and neonatal spleen.