Interleukin 10 induces B lymphocytes from IgA-deficient patients to secrete IgA.
We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete antibodies. However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell differentiation even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce IgM, IgG, and IgA, and Ig levels are further increased by SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but not IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, SAC and anti-CD40 mAb stimulate B cells to differentiate into cells secreting IgG and IgM whereas IL-10 plays a central role in inducing B cells from IgA-D patients to differentiate into IgA secreting cells.
Brière
F
F
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Bridon
J M
JM
Chevet
D
D
Souillet
G
G
Bienvenu
F
F
Guret
C
C
Martinez-Valdez
H
H
Banchereau
J
J
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D017098:IgA Deficiency / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007071:Immunoglobulin A, Secretory; D016753:Interleukin-10