Groups of NZB and NZB/W X-linked (X(id)) 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 X(id) 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 X(id) 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 DNP-Ficoll. Despite the presence of the X(id) gene and the absence of polyclonal B cell activation, approximately 20% of older NZB X(id) mice develop NTA and anti-erythrocyte antibodies. The antibodies to red cells include the IgM and IgG3 isotypes; NTA is entirely IgM. Similarly, NZB/W X(id) 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 IgG3 isotypes. Specific study of autoantibody-producing NZB X(id) and NZB/W X(id) mice revealed such animals were not distinguishable from nonautoantibody-producing NZ X(id) 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 X(id) mice, we attempted to induce autoantibodies by either xenogeneic red cell or DNA immunization. NZB X(id) mice were similar to NZB and produced anti-HB after RRBC immunization. Furthermore, old NZB/W X(id) mice produced antibodies to DNA after immunization with DNA.MBSA in CFA. We conclude that autoantibody production can occur in NZ X(id) mice without apparent alteration in the phenotypic expression of the X(id) 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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Immunology|
|State||Published - 1982|
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