Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses.
Humoral immune responses depend on B cells encountering antigen, interacting with helper T cells, proliferating and differentiating into low-affinity plasma cells or, after organizing into a germinal center (GC), high-affinity plasma cells and memory B cells. Remarkably, each of these events occurs in association with distinct stromal cells in separate subcompartments of the lymphoid tissue. B cells must migrate from niche to niche in a rapid and highly regulated manner to successfully mount a response. The chemokine, CXCL13, plays a central role in guiding B cells to follicles whereas T-zone chemokines guide activated B cells to the T zone. Sphingosine-1-phosphate (S1P) promotes cell egress from the tissue, as well as marginal-zone B-cell positioning in the spleen. Recent studies have identified a role for the orphan receptor, EBV-induced molecule 2 (EBI2; GPR183), in guiding activated B cells to inter and outer follicular niche(s) and down-regulation of this receptor is essential for organizing cells into GCs. In this review, we discuss current understanding of the roles played by chemokines, S1P and EBI2 in the migration events that underlie humoral immune responses.
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, 94143, USA.
João Pedro
JP
Pereira
Lisa M
LM
Kelly
Jason G
JG
Cyster
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002465:Cell Movement; D054382:Chemokine CXCL13 / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D056724:Immunity, Humoral; D008213:Lymphocyte Activation; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology*; D043484:Proprotein Convertases / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D054382:Chemokine CXCL13; C543809:Gpr183 protein, mouse; D043562:Receptors, G-Protein-Coupled; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1