Complement receptor 2/CD21 human naive B cells contain mostly autoreactive unresponsive clones

I Isnardi, YS Ng, L Menard, G Meyers… - Blood, The Journal …, 2010 - ashpublications.org
I Isnardi, YS Ng, L Menard, G Meyers, D Saadoun, I Srdanovic, J Samuels, J Berman…
Blood, The Journal of the American Society of Hematology, 2010ashpublications.org
Abstract Complement receptor 2–negative (CR2/CD21−) B cells have been found enriched
in patients with autoimmune diseases and in common variable immunodeficiency (CVID)
patients who are prone to autoimmunity. However, the physiology of CD21−/lo B cells
remains poorly characterized. We found that some rheumatoid arthritis (RA) patients also
display an increased frequency of CD21−/lo B cells in their blood. A majority of CD21−/lo B
cells from RA and CVID patients expressed germline autoreactive antibodies, which …
Abstract
Complement receptor 2–negative (CR2/CD21) B cells have been found enriched in patients with autoimmune diseases and in common variable immunodeficiency (CVID) patients who are prone to autoimmunity. However, the physiology of CD21−/lo B cells remains poorly characterized. We found that some rheumatoid arthritis (RA) patients also display an increased frequency of CD21−/lo B cells in their blood. A majority of CD21−/lo B cells from RA and CVID patients expressed germline autoreactive antibodies, which recognized nuclear and cytoplasmic structures. In addition, these B cells were unable to induce calcium flux, become activated, or proliferate in response to B-cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. Moreover, gene array analyses of CD21−/lo B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage. Thus, CD21−/lo B cells contain mostly autoreactive unresponsive clones, which express a specific set of molecules that may represent new biomarkers to identify anergic B cells in humans.
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