Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production.
CD5 is a negative regulator of B-cell receptor (BCR) signaling that is up-regulated after BCR stimulation and likely contributes to B-cell tolerance in vivo. However, CD5 is constitutively expressed on the B-1 subset of B cells. Contrary to CD5(-) B-2 B cells, B-1 B cells are long-lived because of autocrine interleukin-10 (IL-10) production through unknown mechanisms. We demonstrate herein a direct relationship between CD5 expression and IL-10 production. Human peripheral blood CD5(+) B cells produce more IL-10 than CD5(-) B cells after BCR activation. Introducing CD5 into CD5(-) B cells induces the production of IL-10 by activating its promoter and the synthesis of its mRNA. The cytoplasmic domain of CD5 is sufficient for this process. CD5 also protects normal human B cells from apoptosis after BCR stimulation while reducing the BCR-induced Ca(2+) response. We conclude that CD5 supports the survival of B cells by stimulating IL-10 production and by concurrently exerting negative feedback on BCR-induced signaling events that can promote cell death.
Gary-Gouy
Hélène
H
Laboratoire d'immunologie, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 543, Paris, France.
Harriague
Julie
J
Bismuth
Georges
G
Platzer
Cornelia
C
Schmitt
Christian
C
Dalloul
Ali H
AH
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D018956:CD5 Antigens / Q000502:physiology*; D020013:Calcium Signaling; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000473:pathology; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D018956:CD5 Antigens; D018076:DNA, Complementary; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10