Studies of congenitally immunologic mutant New Zealand mice. VI. Spontaneous and induced autoantibodies to red cells and DNA occur in New Zealand X-linked immunodeficient (Xid) mice without phenotypic alternations of the Xid gene or generalized polyclonal B cell activation.

Abstract

Groups of NZB and NZB/W X-linked immunodeficient (xid) mice were serially monitored with age and were compared to immunologically intact littermate controls with respect to appearance of autoantibodies, splenic surface markers and immune responsiveness. NZB xid mice have a marked reduction in polyclonal B cell activation as manifested by a reduction in lipopolysaccharide-induced B cell colonies in agar. NZB xid mice, followed for up to 20 mo., have marked reductions in sera levels of IgM and IgG3, an absence or a markedly reduced frequency of cells expressing Lyb-5 and fail to respond to dinitrophenyl [DNP]-Ficoll. Despite the presence of the xid gene and the absence of polyclonal B cell activation, .apprx. 20% of older NZB xid mice develop naturally-occurring thymocytotoxic autoantibody (NTA) and anti-erthrocyte [including anti-HB] antibodies. The antibodies to red cells include the IgM and IgG3 isotypes; NTA is entirely IgM. NZB/W xid female mice have an .apprx. 20% incidence of anti-DNA antibodies at 10 mo. and a 40% frequency at 16 mo. of age; anti-DNA antibodies include IgM and IgG3 isotypes. Specific study of autoantibody-producing NZB xid and NZB/W xid mice revealed such animals were not distinguishable from nonautoantibody-producuing NZ xid mice with respect to levels of IgM and IgG3, frequency of cells that express the Lyb-5 determinant, response to DNP-Ficoll or numbers of B cell colonies. Because of these observations of low frequency autoantibody production in NZ xid mice, attempts were made to induce autoantibodies by either xenogeneic red cell or DNA immunization. NZB xid mice were similar to NZB and produced anti-HB after xid immunization. Old NZB/W xid mice produced antibodies to DNA after immunization with DNA [-methylated bovine serum albumin in complete Freund''s adjuvant]. Thus, autoantibody production can occur in NZ xid mice without apparent alteration in the phenotypic expression of the xid gene. Autoantibodies apparently can appear in NZ mice by mechanisms other than a generalized polyclonal B cell expansion and their appearance is not dependent on the circulating or splenic frequency of the Lyb-5 subset of B cells.