Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis.
OBJECTIVE
Whether and how B lymphocytes contribute to the pathogenesis of spondylarthritis (SpA), a seronegative arthritis associated with gut inflammation, remains unknown. Because innate-like CD5+ B lymphocytes with regulatory functions have been identified in colitis models, we undertook the present study to analyze the presence and function of CD5+ B cells in human SpA.


METHODS
Peripheral blood B cells from patients with SpA, patients with rheumatoid arthritis (RA), and healthy controls were analyzed by flow cytometry. Synovial biopsy samples were evaluated by immunohistochemistry analysis. Sorted CD5+ and CD5- B cells were analyzed for somatic hypermutation, expression of costimulatory molecules, and cytokine production.


RESULTS
The naive, marginal zone-like, and to a lesser extent memory B cell compartments in patients with SpA exhibited a clear and specific increase of CD5+ B cells, which was not found in patients with RA. This increase was not due to either B cell activation or preferential migration of CD5- B cells to the inflamed synovium. Consistent with their phenotype and the low-affinity polyreactive immunoglobulins produced by their murine counterpart cells, CD5+ B cells from patients with SpA showed low levels of somatic hypermutation. With regard to antigen presentation, CD5+ B cells expressed slightly increased HLA-DR levels but low CD80 and CD86 levels. In vitro activation failed to up-regulate these costimulatory molecules but induced significant production of interleukin-10 and interleukin-6 by CD5+ B cells.


CONCLUSIONS
CD5+ B cells are specifically increased in SpA. Analysis of somatic hypermutation, expression of antigen-presenting and costimulatory molecules, and cytokine production indicates that this B cell subset has regulatory capacities. Further investigation of the potential role of CD5+ cells in SpA is warranted.
Academic Medical Center, Amsterdam, The Netherlands.
Tineke
T
Cantaert
Marieke E
ME
Doorenspleet
Gabriela
G
Francosalinas
Jaqueline E
JE
Paramarta
Paul L
PL
Klarenbeek
Yvonne
Y
Tiersma
Chris M
CM
van der Loos
Niek
N
De Vries
Paul Peter
PP
Tak
Dominique L
DL
Baeten
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D025241:Spondylarthritis / Q000276:immunology* / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism
D018956:CD5 Antigens; D015850:Interleukin-6; D016753:Interleukin-10