STAT1-dependent IgG cell-surface expression in a human B cell line derived from a STAT1-deficient patient.
STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expression. Analysis of this point is difficult in humans, as STAT1 deficiency is extremely rare. SD patients die early in childhood from a severe immunodeficiency. Herein, a SD B cell line obtained from a SD patient was compared with a B cell line from a STAT1-proficient subject in search of differences in surface Ig expression. In this SD B cell line, a complete absence of surface IgG was noted. The mRNA encoding the surface form of IgG was detected only in STAT1-proficient B cells; the mRNAs encoding the secreted and the surface forms were detected in SD and STAT1-proficient B cells. Re-expression of STAT1 in SD B cells restored surface IgG expression and a functional BCR. Conversely, shRNA silencing of STAT1 in B cells reduced considerably the expression of the surface IgG. Although limited to one B cell line, these results suggest that STAT1 may play an essential role in surface IgG expression in human B cells. Possible mechanisms involve regulation of mRNA splicing, transcription, or both. These observations extend the role of STAT1 further in adaptive immunity, including the regulation of BCR expression.
Najjar
Imen
I
INSERM, unité 978/Université Paris 13, UFR SMBH 74 rue Marcel Cachin, 93017 Bobigny cedex France.
Deglesne
Pierre-Antoine
PA
Schischmanoff
Pierre Olivier
PO
Fabre
Emmanuelle E
EE
Boisson-Dupuis
Stéphanie
S
Nimmerjahn
Falk
F
Bornkamm
Georg W
GW
Dusanter-Fourt
Isabelle
I
Fagard
Remi
R
D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D015153:Blotting, Western; D002461:Cell Line, Transformed; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics
D007074:Immunoglobulin G; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human