Antigen Receptor Engagement Selectively Induces Macrophage Inflammatory Protein-1α (MIP-1α) and MIP-1β Chemokine Production in Human B Cells

Abstract

Abstract We show herein that B cell Ag receptor (BCR) triggering, but not stimulation by CD40 mAb and/or IL-4, rapidly induced the coordinated expression of two closely related T cell chemoattractants, macrophage inflammatory protein-1β (MIP-1β) and MIP-1α, by human B cells. Naive, memory, and germinal center B cells all produced MIP-1α/β in response to BCR triggering. In contrast to MIP-1α/β, IL-8, which is spontaneously produced by germinal center B cells but not by naive and memory B cells, was not regulated by BCR triggering. Culturing follicular dendritic cell-like HK cells with activated B cells did not regulate MIP-1α/β production, but it did induce production of IL-8 by HK cells. Microchemotaxis assays showed that CD4+CD45RO+ T cells of the effector/helper phenotype actively migrated along a chemotactic gradient formed by BCR-stimulated B cells. This effect was partially blocked by anti-MIP-1β and anti-CC chemokine receptor 5 Ab, but not by anti-MIP-1α Ab suggesting that MIP-1β plays a major role in this chemoattraction. Since maturation of the B cell response to a peptide Ag is mostly dependent on the availability of T cell help, the ability of Ag-stimulated B cells to recruit T cells via MIP-1α/β, may represent one possible mechanism enabling cognate interactions between rare in vivo Ag-specific T and B cells.