The role of Bcl6 in the regulation of transitional B cells and resting mature B cells (P1449)

Abstract As a conserved zinc finger transcription repressor, Bcl6 determines follicular helper T cell differentiation and plays indispensible roles in B cell development and function, especially at the stages of pre-B cell and germinal center B cell. To better understand the role of Bcl6 in B cell lineage, we generate Bcl6 conditional KO mouse by crossing Bcl6 floxed mouse newly made in our lab to CD19cre mouse. Interestingly, B cell development in the bone marrow of conditional KO mice is indistinguishable from control mice. At the transition of T1 B cell to T2 B cell stage, Bcl6 is upregulated and continually maintained in mature B cells. Mainly because of a significant decrease of follicular B cell, conditional KO mice have significantly fewer B220+ cells in spleen compared to control mice. Furthermore, in conditional KO mice, spontaneously-formed GCB cells in Peyer’s patches are decreased dramatically, but there is only slight reduction of GCB cells in spleen after SRBC immunization. The GCB cells in spleen appear to be from incomplete deletion of Bcl6 by CD19cre and by strong proliferation of non-deleted GCB cells. Finally and surprisingly, we detect "truncated Bcl6" in non-GCB cells from Peyer’s patches and spleen in conditional KO mice, which is four times higher than WT Bcl6 in control mice. This indicates an autorepression regulation of Bcl6 in resting mature B cells. Our findings suggest that Bcl6 regulates transitional B cell maturation and maintenance of mature B cell.