In vitro and in vivo functional analysis of CD5⁺ and CD5⁻ B cells of autoimmune NZB × NZW F₁ mice

Abstract

Polyclonal B cell activation has been thought to play the critical role in production of autoantibodies, and possible activation of autoreactive T cells in murine lupus, especially abnormal expansion of CD5⁺ B cells, is one of the characteristic findings in these mice. The aim of this study was to investigate further the characteristics and function of CD5⁺ and CD5⁻ B cells. Both CD5⁺ and CD5⁻ B cells were isolated for in vitro autoantibody production, cytokine expression and in vivo anti-DNA antibody production with the reconstitution of severe combined immunodeficient (SCID) mice. The data showed: (i) both CD5⁺ and CD5⁻ B cells produced a high level of anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5; (ii) both peritoneal CD5⁺ and CD5⁻ B cells expressed a high level of IL-10 mRNA after stimulation with LPS, while in contrast CD5⁻ B cells of non-autoimmune BALB/c mice did not express IL-10 mRNA after stimulation; (iii) SCID mice reconstituted with either CD5⁺ or CD5⁻ B cells all produced significant levels of anti-DNA antibodies in vivo and manifested with proteinuria. These data suggest both CD5⁺ and CD5⁻ B cells play important roles in polyclonal B cell activation and subsequent autoantibody production. Generalized polyclonal B cell activation, instead of expanding a certain subpopulation of B cells, contributed to the pathogenesis of autoimmunity in murine lupus.

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