Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection.
Features of the lymphocyte population in systemic lupus erythematosus (SLE) include a disordered B cell profile and production of autoantibodies. An additional distinctive perturbation is the overexpression of V4-34-encoded serum immunoglobulins (Ig). A similar rise in V4-34-encoded Ig occurs in normal subjects following infection with certain herpesviruses, and is found in Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). To assess common and distinctive features of B cells in patients with SLE and IM, we compared the B cell profile and V4-34 gene involvement in patients with SLE and IM. B cell profiles from patients with IM paralleled those of patients with SLE, showing a differential loss of naïve and memory B cells and the maintenance of plasmablast/early plasma cells. Class-switched V4-34-encoded IgG from plasmablast/early plasma cells was evident both in patients with SLE and IM and revealed common features of oligoclonal expansions with most having undergone somatic hypermutation. It has been proposed that, in healthy individuals, expression of the V4-34 gene is specifically censored prior to isotype switch as a control on autoreactivity. If so, censoring is bypassed following EBV infection, after which equilibrium is restored. Continuing high serum levels in SLE may arise either by disordered regulation, or by subclinical reactivation of endogenous virus.
Mockridge
C Ian
CI
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Tremona Road, Southampton SO16 6YD, UK.
Rahman
Anisur
A
Buchan
Sarah
S
Hamblin
Terry
T
Isenberg
David A
DA
Stevenson
Freda K
FK
Potter
Kathleen N
KN
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000097:blood / Q000235:genetics*; D007244:Infectious Mononucleosis / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D007135:Immunoglobulin Variable Region; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7