Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b(+)CD11c(+) dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB x NZW)F1 (BWF1 ) mice developing lupus nephritis, but not in similarly aged NZB and NZW mi ce. BLC-positive cells were present in the cellular infiltrates in the targ et organs with a reticular pattern of staining. CD11b(+)CD11c(+) dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identif ied as the major cell source for BLC. CD4(+) T cells as well as B cells wer e dramatically increased in the thymus in aged BWF1 mice, whereas no increa se was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was sig nificantly higher than those in the spleen and peripheral blood in aged BWF 1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cel l surface CXCR5 expression on B1 cells was significantly higher than that o n B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cell s in the target organs in aged BWF1 mice may play a pivotal role in breakin g immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus.