Helper B cells promote cytotoxic T cell survival and proliferation independently of antigen presentation through CD27/CD70 interactions.
CD8-expressing cytotoxic T cell (CTL) interactions with APCs and helper T cells determine their function and ability to survive. In this study, we describe a novel interaction independent of Ag presentation between activated CTLs and bystander CD19-expressing B lymphocytes. Ag-stimulated CTLs serially engage autologous B lymphocytes through CD27/CD70 contact that promotes their survival and proliferation. Moreover, these interactions induce the release of proinflammatory cytokines that follows two general patterns: 1) an epitope-dependent enhancement of cytokine release, and 2) a previously undiscovered coordinate release of cytokines independent of epitope exposure. The latter includes chemoattractants targeting activated T cells. As a result, activated T cells are attracted to B cells, which exert a "helper" role in lymphatic organs or in areas of inflammation. This observation provides a mechanistic explanation to previously reported experimental observations suggesting that B cells are required for T cell priming in vivo.
Deola
Sara
S
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Panelli
Monica C
MC
Maric
Dragan
D
Selleri
Silvia
S
Dmitrieva
Natalia I
NI
Voss
Ching Y
CY
Klein
Harvey
H
Stroncek
David
D
Wang
Ena
E
Marincola
Francesco M
FM
D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D053282:CD27 Ligand / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005452:Fluoresceins / Q000032:analysis; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D013388:Succinimides / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D053282:CD27 Ligand; D016207:Cytokines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D013388:Succinimides; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7