Cytokine control of memory B cell homing machinery.
The germinal center (GC) is a pivotal site for the development of B cell memory. Whereas GC B cells do not chemotax to most chemokines and do not express the adhesion receptors L-selectin, alpha(4)beta(7), and cutaneous lymphocyte Ag (CLA), memory B cells respond to various chemotactic signals and express adhesion receptors. In this study, we show that CD40 ligand, IL-2, and IL-10 together drive this transition of GC B cells to memory phenotype in vitro, up-regulating memory B cell markers, chemotactic responses to CXC ligand (CXCL)12, CXCL13, and CCL19, and expression of adhesion receptors L-selectin, alpha(4)beta(7), and CLA. Moreover, addition of IL-4 modulates this transition, preventing chemotactic responses to CXCL12 and CXCL13 (but not to CCL19), and inhibiting the re-expression of L-selectin, but not of CLA or alpha(4)beta(7). CCR7 expression, responsiveness to CCL19, and L-selectin/alpha(4)beta(7) phenotype are coordinately regulated. Thus, IL-2/IL-10 and IL-4 play important and distinctive roles in developing the migratory capacities of memory B cells.
Roy
Meenakshi P
MP
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. mroy@microbio.ucla.edu
Kim
Chang H
CH
Butcher
Eugene C
EC
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D023201:CD40 Ligand / Q000494:pharmacology; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000494:pharmacology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects / Q000378:metabolism
C515460:CCL19 protein, human; C515255:CXCL12 protein, human; C110663:CXCL13 protein, human; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4