A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE.
We previously reported that some systemic lupus erythematosus (SLE) patients have a population of circulating memory B cells with >2-fold higher levels of CD19. We show here that the presence of CD19(hi) B cells correlates with long-term adverse outcomes. These B cells do not appear anergic, as they exhibit high basal levels of phosphorylated Syk and ERK1/2, signal transduce in response to BCR crosslinking, and can become plasma cells (PCs) in vitro. Autoreactive anti-Smith (Sm) B cells are enriched in this population and the degree of enrichment correlates with the log of the serum anti-Sm titer, arguing that they undergo clonal expansion before PC differentiation. PC differentiation may occur at sites of inflammation, as CD19(hi) B cells have elevated CXCR3 levels and chemotax in response to its ligand CXCL9. Thus, CD19(hi) B cells are precursors to anti-self PCs, and identify an SLE patient subset likely to experience poor clinical outcomes.
Nicholas
Matilda W
MW
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dooley
Mary Anne
MA
Hogan
Susan L
SL
Anolik
Jennifer
J
Looney
John
J
Sanz
Ingnacio
I
Clarke
Stephen H
SH
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000097:blood / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000097:blood / Q000276:immunology; D000069283:Rituximab; D055517:snRNP Core Proteins
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D001324:Autoantigens; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D007155:Immunologic Factors; D054367:Receptors, CXCR3; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000069283:Rituximab