Expanded population of activated antigen-engaged cells within the naive B cell compartment of patients with systemic lupus erythematosus.
Polyclonal B cell activation is a well-described feature of systemic lupus erythematosus (SLE), but the immune mechanisms leading to this activation are unclear. To gain insight into these processes, we extensively characterized the activated peripheral blood B cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various combinations of conjugated Ab to identify distinct peripheral B cell subsets, and activation was assessed by measurement of forward scatter and CD80 or CD86 expression using flow cytometry. SLE patients had altered proportions of several B cell subsets, many of which demonstrated increased activation as assessed by forward scatter. This activation occurred at an early developmental stage, as B cells in the transitional (T2) stage were already significantly larger than those seen in controls. Increased proportions of CD80- or CD86-expressing cells were also seen in multiple B cell subsets, with the most striking differences observed in the naive CD27-CD23+ population. Within the CD23+ subset, increased costimulatory molecule expression was most pronounced in an IgD+IgMlow population, suggesting that activation follows Ag engagement. Although controls also had IgD+IgMlowCD23+ cells, they were reduced in number and not activated. Thus, there is an altered response to Ig receptor engagement with self-Ags in lupus.
Chang
Nan-Hua
NH
Arthritis Centre of Excellence, Toronto Western Hospital Research Institute, and Department of Medicine, University of Toronto, Ontario, Canada.
McKenzie
Tamara
T
Bonventi
Gabriel
G
Landolt-Marticorena
Carolina
C
Fortin
Paul R
PR
Gladman
Dafna
D
Urowitz
Murray
M
Wither
Joan E
JE
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male
D001324:Autoantigens; D053264:B-Cell Activating Factor; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha