Session Title: B-cell Biology and Targets in Autoimmune Disease
Session Type: Abstract Submissions (ACR)
Primary Sjögren’s syndrome (pSS) is the autoimmune disease associated with the higher risk of developing non-Hodgkin lymphoma.
Objective: To determine the nature of B cells driving lymphoproliferation in pSS.
B cell subsets and function were analyzed in peripheral blood from 66 adult patients with pSS [including 15 patients with B-cell lymphoproliferative disorder (LPD)] and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. We tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from pSS-LPD.
We report here the expansion of an unusual CD21-/low B-cell population which correlates with lymphoproliferation in pSS patients. A majority of CD21−/low B cells from pSS patients expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment because their immunoglobulin genes were mutated. They 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. However, CD21−/low B cells from pSS remained responsive to TLR9 stimulation. Gene array analyses of CD21−/low B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage.
pSS patients who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible for developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.
J. Bannock Sr.,
T. Vazquez Sr.,
C. Massad Sr.,
F. Joly Sr.,
M. Rosenzwajg Sr.,
D. Sene Sr.,
P. Benech Sr.,
D. Klatzmann Sr.,
E. Meffre Sr.,
P. Cacoub Sr.,
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/expansion-of-autoreactive-unresponsive-cd21-low-b-cells-in-sjogrens-syndrome-associated-lymphoproliferation/