Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

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« 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/