Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients.
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD-CD27-(double negative, DN) and CD21-CD11c+(CD21low) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21lowB cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21low(9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients. The majority of DN B cells had an IgG+memory phenotype, whereas CD21lowB cells consisted of a mixed population of CD27-naive, CD27+memory, IgG+, and IgM+cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class-switched memory B cells and intermediate costimulatory molecule expression between naive and class-switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21lowB cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age-associated B cells. DN and CD21lowB cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines.
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.
Nele
N
Claes
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.
Judith
J
Fraussen
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.
Marjan
M
Vanheusden
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.
Niels
N
Hellings
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.
Piet
P
Stinissen
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium.|Rehabilitation and MS-Center, B-3900 Overpelt, Belgium.
Bart
B
Van Wijmeersch
Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, 6229 ER Maastricht, the Netherlands; and.|Department of Neurology, Academic MS Center Limburg, Zuyderland Medical Center, 6162 BG Sittard, the Netherlands.
Raymond
R
Hupperts
Biomedical Research Institute, Hasselt University and School of Life Sciences, Transnational University Limburg, 3590 Diepenbeek, Belgium; veerle.somers@uhasselt.be.
Veerle
V
Somers
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007156:Immunologic Memory; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
D007072:Immunoglobulin D; D018836:Inflammation Mediators; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7