Antigen receptor engagement selectively induces macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta chemokine production in human B cells.
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-1 beta (MIP-1 beta) and MIP-1 alpha, by human B cells. Naive, memory, and germinal center B cells all produced MIP-1 alpha/beta in response to BCR triggering. In contrast to MIP-1 alpha/beta, 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-1 alpha/beta 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-1 beta and anti-CC chemokine receptor 5 Ab, but not by anti-MIP-1 alpha Ab suggesting that MIP-1 beta 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-1 alpha/beta, may represent one possible mechanism enabling cognate interactions between rare in vivo Ag-specific T and B cells.
Krzysiek
R
R
Institut National de la Santé et de la Recherche Médicale, Unit 131, Institut Paris-Sud sur les Cytokines, Clamart, France.
Lefèvre
E A
EA
Zou
W
W
Foussat
A
A
Bernard
J
J
Portier
A
A
Galanaud
P
P
Richard
Y
Y
D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002648:Child; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D016209:Interleukin-8 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D019013:CD40 Antigens; D054407:Chemokine CCL4; D007075:Immunoglobulin M; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM