Spontaneous acquisition of plasma cell phenotype in DT40 B cells with inactivation of Bcl-6

: Alinikula J, Mustonen L, Nera KP, Lassila O

: Sirpa Jalkanen, Jaan Lindgren

: Scandinavian Society for Immunology 37th Annual Meeting

Publisher: BLACKWELL PUBLISHING

: 2007

: Scandinavian Journal of Immunology

: SCANDINAVIAN JOURNAL OF IMMUNOLOGY

: SCAND J IMMUNOL

: 65

: 6

: 591

: 1

: 0300-9475

B-cell lymphoma 6 (Bcl-6) is implicated in diffuse large cell lymphoma generation, where chromosomal transloca-tions result in constitutive expression of the gene. Bcl-6 is highly expressed in germinal center cells, but the pro-tein is virtually absent in resting B-cells. Gene targeting studies in mice have revealed the necessity of Bcl-6 forgerminal center formation. Mitogenic signaling in B cells induces Bcl-6 production that is needed to keep prdm1,the gene encoding Blimp-1, and subsequent plasma cell differentiation repressed. Our previo us studies haveshown that Pax5 represses plasma cell differentiation and maintains Bcl-6 mRNA expression. We targeted theN-terminal half of the Bcl-6 gene in DT40 cell line to obtain Bcl-6 knockout cells. We found that Bcl-6 repres-ses prdm1 and that the expression of genes encoding proteins of secretory machinery is upregulated in theabsenc e of Bcl-6. The Bcl-6 was found to be needed also for maintenance of Pax5 and AID expression in thesecells. The results suggest that loss of Bcl-6 promotes plasma cell differentiation in the absence of external stimuli.