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

Abstract Groups of NZB and NZB/W X-linked (Xid) immunodeficient 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 LPS-induced B cell colonies in agar. Moreover, NZB Xid mice, followed for up to 20 mo, have marked reductions in sera levels of IgM and lgG3, an absence or a markedly reduced frequency of ceils expressing Lyb-5, and fail to respond to DNP-Ficoll. Despite the presence of the Xid gene and the absence of polyclonal B cell activation, approximately 20% of older NZB Xid mice develop NTA and anti-erthrocyte antibodies. The antibodies to red cells include the IgM and lgG3 isotypes; NTA is entirely IgM. Similarly, NZB/W Xid female mice have an approximately 20% incidence of anti-DNA antibodies at 10 mo and a 40% frequency at 16 mo of age; anti-DNA antibodies include IgM and lgG3 isotypes. Specific study of autoantibody-producing NZB Xid and NZB/W Xid mice revealed such animals were not distinguishable from nonautoantibody-producing NZ Xid mice with respect to levels of IgM and lgG3, 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, we attempted to induced autoantibodies by either xenogeneic red cell or DNA immunization. NZB Xid mice were similar to NZB and produced anti-HB after RRBC immunization. Furthermore, old NZB/W Xid mice produced antibodies to DNA after immunization with DNA.MBSA in CFA. We conclude that autoantibody production can occur in NZ Xid mice without apparent alteration in the phenotypic expression of the Xid gene. This suggests that autoantibodies can appear in NZ mice by mechanisms other than a generalized polyclonal B cell expansion, and is not dependent on the circulating or splenic frequency of the Lyb-5 subset of B cells.