CD40-activated B cells from patients with systemic lupus erythematosus can be modulated by therapeutic immunoglobulins in vitro.
BACKGROUND
Aberrant signaling within and between B and T cells, considered to be central in systemic lupus erythematosus (SLE), could depend on enhanced CD40-CD154 activation. As a result, autoreactive B cells, normally anergic, differentiate and secrete antibodies attacking several normal tissues. Thus restorating B cell homeostasis might help control this disease. In this study, two facets of SLE B cells were investigated, namely their in vitro response to CD40-CD154 and the effect of treatment with human immunoglobulins for intravenous use (IVIg).


METHODS
Blood samples from SLE patients and healthy volunteers were obtained and used to isolate B cells, which were activated through CD40 in the presence or absence of IVIg. The phenotype, proliferation, and differentiation of the SLE B cells were determined and compared with those of control B cells using flow cytometry and standard ELISA.


RESULTS
In this model, CD40-activated SLE B cells, as control B cells, proliferated and differentiated and were characterized by the emergence of CD19(lo)CD38(++)CD138(+)CD27(++) cells. IVIg treatment of the CD40-activated SLE B cells resulted in higher differentiation, characterized by increased secretion rates of IgG and IgM, as reported previously for control B cells.


CONCLUSIONS
Taken as a whole, such accelerated differentiation of CD40-activated B cells suggests that IVIg may participate in re-equilibration of the antibody repertoire by replacing pathological antibodies by de novo harmless antibodies.
Recherche et développement, Héma-Québec, Ingénierie cellulaire, 1070, avenue des Sciences-de-la-vie, Québec, QC G1V 5C3, Canada. sonia.neron@hema-quebec.qc.ca
Sonia
S
Néron
Gilles
G
Boire
Nathalie
N
Dussault
Claudia
C
Racine
Artur J
AJ
de Brum-Fernandes
Serge
S
Côté
Annie
A
Jacques
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D000943:Antigens, Differentiation; D016756:Immunoglobulins, Intravenous