Dissecting the role of proinflammatory chemokine CCL3 in the selection of germinal center B cells and in secondary antibody responses

Abstract

Abstract Expression of CCL3 and CCL4 chemokines is upregulated in B cells upon crosslinking of B cell receptors and in germinal center (GC) centrocytes. However, the role of these proinflammatory chemokines in B cell responses is still unclear. Single cell qPCR analysis suggests that only a small fraction of GC centrocytes upregulates expression of CCL3/4. While B cell-intrinsic production of CCL3 promotes B cell interactions and negative control by follicular regulatory T cells at the peak of GC response, at the later stages of GC response it promotes B cells selection. Consistent with that, secondary antibody responses in CCL3 knockout mice are reduced. Our findings suggest that CCL3 is involved into multifaceted regulation of GC responses. Analyses of the mechanisms promoting both the negative and positive regulation of GC B cells in CCL3-dependent fashion are underway. These studies should be important for dissecting the role of CCL3 in normal immune responses and in B cell-originated lymphomas, where CCL3/4 are often elevated.