The ability of synoviocytes to support terminal differentiation of activated B cells may explain plasma cell accumulation in rheumatoid synovium.
To understand the accumulation of plasma cells within RA synovium, the ability of rheumatoid synoviocytes to support the differentiation of B cells into plasma cells was explored. Tonsillar B lymphocytes cultured over confluent monolayers of synoviocytes, secreted threefold more Igs (mainly IgM) than B cells cultured directly on plastic well. More importantly, synoviocytes enhanced by 14-fold the production of Igs (mainly IgG) by B cells costimulated with Staphylococcus aureus Cowan (SAC) particles. IL-10 and, in a lower extent, IL-2 increased Ig secretion in cocultures, and their combination was synergistic. In the presence of SAC, IL-2, and IL-10, synoviocytes increased by 13-884-fold the production of IgG, which reached 0.19 ng/cell per day. RA as well as normal synoviocytes were more potent than other adherent cell lines to support terminal B cell differentiation. Synoviocyte activity involved both a support of B cell survival, and an induction of the terminal differentiation of B cells into mature plasma cells with typical morphology, high levels of intracytoplasmic Igs, and CD20- CD38high surface expression. The present observation should permit the identification of molecules involved in the maturation of B cells into plasma cells, and in their accumulation in rheumatoid synovium.
Dechanet
J
J
Schering-Plough Laboratory for Immunological Research, Dardilly, France.
Merville
P
P
Durand
I
I
Banchereau
J
J
Miossec
P
P
D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10