Conditional Knockout of Sox4 Markedly Affects B Lymphopoiesis in Adult Mice.

Abstract 2524

Poster Board II-501

B cells constitute an integral part of the immune system. The development of mature B cells from hematopoietic stem cells is a complex process that is regulated in a hierarchical order by various proteins, particularly transcription factors. Sox4 is a SRY-related HMG box containing transcription factor and is known to be involved in B cell development. However, the role of Sox4 in various stages of B cell development has not been systematically investigated. In this study we used a conditional knockout mouse strain and studied the effect of Sox4 deletion in B lymphopoiesis in adult mice. We crossed the Sox4-floxed mice with different Cre mouse strains that were expected to delete the floxed Sox4 gene at different B cell developmental stages. These Cre strains included Vav-iCre (expressed in hematopoietic stem cell stage, starting from early embryos), MX1-Cre (expression in hematopoietic stem cells, induced by pIpC injection in adults), MB1-Cre (expressed in B cells, starting from early progenitor cells in embryos), and CD21-Cre (expressed in mature B cells). We demonstrated that deletion of Sox4 caused an arrest of B lymphopoiesis at the transition from pre-pro-B cell (fraction A) stage to pro-B cell stage (fraction B): fraction A cells are slightly reduced in number whereas fraction B and later stage cells are nearly absent. The pre-pro-B cells from the Sox4 knockout mice retain a population of AA4.1+ cells, which are considered to be developed into B cells. Deletion of Sox4 in early embryonic stage (Vav-iCre) or in adults (Mx1-Cre) results in a similar phenotype on B lymphopoiesis, except that peritoneal B1 cells appear to be affected with Vav-iCre, but not with Mx1-Cre. MB1-Cre gave rise to similar results as did Vav-iCre, but the arrest was not as dramatic as with Vav-iCre. CD21-Cre produced no significant difference in B cell phenotype. These data suggested that Sox4 is required for early B cell development at the transition from pre-pro-B cells to pro-B cells and is not required for mature B cells. We are currently investigating the transcription program of this transcription factor in B cell development.