Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype.

Abstract

Lymph node and spleen cells of the autoimmune MRL/MP-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. Lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-.mu. or lipopolysaccharide [LPS from Salmonella minnesota]. MRL/1 mice begin producing the factor as early as 1 mo. of age, but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2- phenotype. Because of its association with the lpr/lpr genotye, this B cell differentiation factor is termed L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). The increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/1-derived supernatants. L-BCDF induces both IgM and IgG synthesis in LPS-activated B cells; it has a greater effect on IgG secretion. The production of IgG1, IgG2a and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE [systemic lupus erythematosus] mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.