Role of the TAM receptor Axl in differentiation and activation of B cells (P4058)

Abstract

Abstract In dendritic cells (DCs), TLR activation upregulates TAM receptor expression and these TAM receptors initiated pathways subsequently shut down cytokine production. Moreover, TAM receptor deficient mice develop a severe SLE-like disease. TLR9 and TLR7 play a key role in the detection of autoantigens by both DCs and B cells in the context of systemic autoimmunity. To better understand the direct effects of TAM receptors on B cells, we have used BCR Tg mice (AM14) that recognize autologous IgG2a. AM14 B cells are activated by immune complexes (ICs) that incorporate either DNA or RNA through pathways dependent on TLR9 and TLR7, respectively. Contrary to DCs, expression of the TAM receptor Axl is not induced by TLR ligands but is dependent on crosslinking of the BCR per se. However, BCR/TLR9, but not BCR/TLR7, co-engagement inhibits Axl upregulation, pointing to a role for TLR9 in the regulation of Axl expression. Activation of AM14 B cells by RNA-containing ICs induces TLR7-dependent differentiation into plasma cells and these plasma cells express high levels of Axl. In contrast, BCR/TLR9-dependent activation of AM14 B cells by DNA-containing ICs blocks Axl expression and does not lead to plasma cell differentiation. These data identify unique outcomes of BCR/TLR7 and BCR/TLR9 co-engagement on B cell differentiation and Axl expression. Furthermore, these B cell intrinsic responses may account for the opposing roles of TLR7 and TLR9 in the regulation of systemic autoimmunity.