B cell expression of the inhibitory Fc gamma receptor is unchanged in early MS.
Expression of the inhibitory Fcgamma receptor IIB (FcgammaRIIB) has emerged as a late checkpoint during peripheral B cell development which prevents autoreactive memory B lymphocytes from becoming long-lived plasma cells. Decreased expression of FcgammaRIIB or non-functional FcgammaRIIB variants are associated with the development of autoimmune tissue inflammation. We determined the expression profile of FcgammaRIIB in peripheral blood cells in treatment-naïve patients with early MS. Twenty-five patients with clinically isolated syndrome (CIS) who converted to clinically definite MS (CDMS) and 25 demographically matched healthy donors were included in the study. Frequencies of peripheral blood monocytes and B cell subsets as well as FcgammaRIIB expression profile was determined by flow cytometry. FcgammaRIIB expression levels were higher in B cells compared to monocytes (p<0.0001) and higher in memory B cells compared to their naïve counterparts (p<0.0001). However, FcgammaRIIB expression in naïve and memory B cells as well as monocytes was unchanged in patients with early MS at onset of symptoms as well as after conversion to CDMS compared to controls. No significant correlations were found between FcgammaRIIB expression levels and brain MRI-derived metrics or EDSS progression during follow-up. These data indicate that FcgammaRIIB expression, a critical late B cell differentiation checkpoint preventing the occurrence of autoreactive long-lived plasma cells, is not impaired in treatment-naïve patients with MS, at least in the early phases of the disease.
Comabella
Manuel
M
Centre d'Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d Hebron (HUVH), Barcelona, Spain. mcomabella@ir.vhebron.net
Montalban
Xavier
X
Kakalacheva
Kristina
K
Osman
Deeqa
D
Nimmerjahn
Falk
F
Tintoré
Mar
M
Lünemann
Jan D
JD
D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000276:immunology*; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013577:Syndrome; D013997:Time Factors; D055815:Young Adult
C499173:FCGR2B protein, human; D006131:Growth Inhibitors; D017452:Receptors, IgG