Background/Purpose: With the advent of B cell targeted therapies the modulation of memory B cells seems to be a prime target. Human peripheral memory B cells can be distinguished by the phenotypic expression of CD27 and IgD defining three major B cell subpopulations: CD27+IgD+ pre-switch, CD27+IgD- post-switch and CD27-IgD- double negative memory B cells. We analyzed these different memory populations in RA and under IL6-R blockade.

Methods: B cells were phenotypically analyzed from RA patients at baseline, week 12 and week 24 under tocilizumab (TCZ) treatment. Memory B cell subsets were defined by CD27 and IgD and were further analyzed by color flow cytometry for surface staining of CD95, intracellular ki-67 and CXCR3 expression.

Results: The phenotypically analyzed profile in RA patients (n=60) and healthy donors (n=20) revealed that the memory B cells are activated and have higher expression of CXCR3. Surface and intracellular staining of B cells showed a significantly higher percentage of CD95 (p=0.01), ki-67 (p=0.04) and CXCR3 (p= 0.03) expression in RA. CD95 & ki-67 expressions were highest in post-switch memory B cells while CXCR3 expression was highest in pre-switch. The expressions of ki-67, CD95 and CXCR3 were significantly reduced during IL-6R blockade (Tocilizumab) therapy at week 12 & 24 in all B cell subsets.

Conclusion: Our data suggests that the three major peripheral memory B cell populations, pre-, post-switch and double negative B cells are activated in RA with enhanced CD95, Ki-67 and CXCR3 expressions compared to healthy individuals. These higher expressions in all memory B cell subsets can be reduced by IL-6R inhibition in vivo.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytokines-inhibition-modulates-activation-and-homing-receptor-of-different-peripheral-memory-b-cell-subsets-in-ra/