Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: a mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies.
Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial effects of IVIg in primary immunodeficiencies are not completely understood. Therefore we investigated the effect of 'replacement dose' of IVIg by probing its action on B cells from CVID patients. We demonstrate that IVIg at low doses induces proliferation and immunoglobulin synthesis from B cells of CVID patients. Interestingly, B cell stimulation by IVIg is not associated with induction of B cell effector cytokine IFN-γ and of transcription factor T-bet. Together, our results indicate that in some CVID patients, IVIg rectifies the defective signaling of B cells normally provided by T cells and delivers T-independent signaling for B cells to proliferate. IVIg 'replacement therapy' in primary immunodeficiencies is therefore not a merepassive transfer of antibodies to prevent exclusively the recurrent infections; rather it has an active role in regulating autoimmune and inflammatory responses through modulating B cell functions and thus imposing dynamic equilibrium of the immune system.
Institut National de la Santé et de la Recherche Médicale Unité 872, F-75006 Paris, France. jagadeesh.bayry@crc.jussieu.fr
Jagadeesh
J
Bayry
Emilie M
EM
Fournier
Mohan S
MS
Maddur
Janakiraman
J
Vani
Bharath
B
Wootla
Sophie
S
Sibéril
Jordan D
JD
Dimitrov
Sébastien
S
Lacroix-Desmazes
Mikael
M
Berdah
Yoann
Y
Crabol
Eric
E
Oksenhendler
Yves
Y
Lévy
Luc
L
Mouthon
Catherine
C
Sautès-Fridman
Olivier
O
Hermine
Srini V
SV
Kaveri
D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D017074:Common Variable Immunodeficiency / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D016756:Immunoglobulins, Intravenous