Differential involvement of the transcription factor Blimp-1 in T cell-independent and -dependent B cell differentiation to plasma cells

Along humoral immune responses, different stimuli drive the differentiation of B lymphocytes to Ig-secreting plasma cells in discrete microenvironment s, The Blimp-1 transcription factor is up-regulated early during the transi tion of mature B cells to IgM-secreting plasma cells. In the present study, we have examined the requirement of Blimp-1 in plasma cell formation after both T cell-independent (LPS) and -dependent (CD40 + IL-4, Th cell lines) stimulation of spleen B cells. B lymphocyte-induced maturation protein (Bli mp-1) was expressed early after in vitro LPS stimulation, mainly in a popul ation of IgM(+)Syndecan(+)CD43(+) preplasma cells. In contrast, the BSAP tr anscription factor expressed in mature B cells was down-regulated during th e differentiation to plasma cells, Treatment of these cultures with Blimp-1 -specific antisense phosphorothioate oligonucleotides suppressed both Blimp -1 protein levels and the emergence of IgM(+)Syndecan(+) cells and plasma c ells. However, T-B cell cocultures of spleen B cells from C3H/HeJ (H-2(k)) mice and syngeneic autoreactive SR.10 Th2 cells submitted to the anti-Blimp -1 therapy did not show any significant reduction in IgM- and IgG1-secretin g plasma cell formation. Spleen B cells treated with anti-CD40 mAb + IL-4 d ifferentiated to IgG1-secreting cells without significant transcription of the Blimp-1 gene; anti-Blimp-1 treatment subsequently did not have any effe ct in the later cultures. Altogether, these results suggest that Blimp-1 tr anscription factor specifically promotes T cell-independent B cell differen tiation to plasma cells, probably at preplasma cell stages. In contrast, T cell-dependent plasma cell formation likely evolves through Blimp-1-indepen dent pathways.