In Vitro Studies of the Genetically Determined Unresponsiveness to Thymus-Independent Antigens in CBA/N Mice

Abstract

The X-chromosome-linked B lymphocyte defect of CBA/N mice has been studied in vitro by comparing the ability of (CBA/N × DBA/2)F₁ (X^-/X^- × X⁺/Y) male (X^-/Y) and female (X^-/X⁺) spleen cells to respond to the thymus-independent antigen DNP (or TNP)-AECM-Ficoll. (CBA/N × DBA/2)F₁ male spleen cells failed to generate significant in vitro anti-TNP antibody responses to DNP- or TNP-AECM-Ficoll, in contrast to spleen cells from F₁ female (X^-/X⁺) mice which responded normally to these T-independent antigens. Spleen cells from male F₁ mice responded almost as well as F₁ female cells to the thymus-dependent antigen, TNP-sheep red blood cells (TNP-SRBC) in vitro. Adding F₁ male cells to F₁ female cells failed to reduce the response of the latter to DNP-AECM-Ficoll, suggesting that the inability of F₁ male cells to respond was not due to active suppression. The response of F₁ male spleen cells to TNP-SRBC was not impaired by adding high concentrations of TNP-AECM-Ficoll indicating that the mechanism of unresponsiveness was not tolerance induction in all TNP-specific precursors. Lymphocytes from F₁ male mice were capable of forming anti-TNP antibody after stimulation with lipopolysaccharide (LPS) in high concentrations; DNP-AECM-Ficoll had no effect no this polyclonal response. B lymphocytes from mice bearing only the X-chromosome of the CBA/N strain thus display a profound defect in B cell activation. This functional defect may represent either an inability of the defective B cells to be activated by thymus-independent antigens or the absence of a sub-class of B cells which respond to thymus-independent antigens.