ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 2667

Activated Memory B Cell Compartment in Rheumatoid Arthritis: Impact of B Cell Depletion Therapy

Diana G. Adlowitz1, Jennifer Hossler1, Jamie Biear2, Christopher A. Cistrone1, Teresa Owen1, Wensheng Wang1, Arumugam Palanichamy1, Ignacio Sanz3 and Jennifer H. Anolik1, 1Medicine- Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, 2Allergy, Immunology and Rheumatology, University of Rochester, Rochester, NY, 3Allergy, Immunology and Rheumatology, Emory University School of Medicine, Atlanta, GA

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: B cells and rheumatoid arthritis (RA)

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis II: Cellular Effectors of Rheumatoid Arthritis and Novel Rheumatoid Arthritis Genome-Wide Association Studies

Session Type: Abstract Submissions (ACR)

Background/Purpose: B cells are critical players in the orchestration of properly regulated immune responses.  This is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions, a balance that we postulate is perturbed in autoimmune diseases such as RA and may be corrected after B cell depletion therapy (BCDT).

Methods: B cells from 13 RA patients were analyzed by multi-color flow cytometry at baseline and longitudinally after BCDT. Expression of CXCR3, CD21, CD95, and anchor markers (IgD, CD19, CD27, CD38, CD24 and live/dead/T-cell exclusions) were used to subset memory B cells.  Expression of MitoTracker Green extrusion, CD10, IgM, CD23 and anchor markers were used to subset transitional B cells. RA patients met ACR criteria for classification, and activity was assessed based on DAS28. Cytokine expression in distinct purified B cell subsets or total B cells in PBMCs were examined by flow cytometry after 88 hours stimulation (CpG 2006, anti-CD40, IL2, and BAFF) and 5 hr culture with PMA and ionomycin.

Results: In RA patients both CD27+IgD- switched memory (SM) and CD27-IgD- double negative memory (DN) contained higher fractions of CD95+ and CD21- activated B cells (DN CD95+: RA 28.9+3.9 vs. HC 10.7+1.2, p<0.0001; DN CD21-: RA 41.6+7.3 vs. HC 27.3+2.7, p=0.03). After BCD (1 month) the predominant B cell populations were memory (increase in DN from baseline 6.9+4.4 vs. 1 month 47.7+29.7, p=0.007; SM baseline 14.2+9.7 vs. 1 month 36.1+25.9, p=0.05).  Notably, the residual memory B cells displayed a high fraction of CD95+ (DN 59.4+20.3, SM: 52.8+16.3) and CD21- (DN 94.6+2.9, SM: 73.1+22.2) compared to pre-depletion (CD95+: DN 28.9, p=0.03; SM: 38.7+18.0, p=0.1; CD21-: DN 41.6, p=0.0005; SM: 24.9, p=0.006;) suggesting some resistance of these activated populations to anti-CD20. Reconstitution occurred between 4 and 12 months with a variable distribution of transitional, naïve, and memory B cell subsets. At a reconstitution time-point (12 month), the fraction of activated memory remained high (CD95+ SM 91.4+4.6, p=0.001 vs. baseline; CD21- SM  70.4+12.4, p=0.009 vs. baseline), but there was a shift to a naïve/transitional dominant B cell compartment. The critical role of B cells as secretors of cytokines in a polarized fashion was highlighted by the propensity of CD27+ memory B cells to produce pro-inflammatory (TNF) over regulatory (IL10) cytokines (TNF: SM 28.2+5.4% vs. transitional 13.6+2.9, p=0.05; IL10: SM 3.5+0.7 vs. transitional 9.8+1.5, p=0.008). The effects of BCD on B cell cytokine secretion are under investigation.

Conclusion: Our results support the hypothesis that the clinical and immunological outcome of B cell depletion therapy depends on the relative balance of protective and pathogenic B cell subsets established after B cell depletion and upon B cell repopulation.


Disclosure:

D. G. Adlowitz,
None;

J. Hossler,
None;

J. Biear,
None;

C. A. Cistrone,
None;

T. Owen,
None;

W. Wang,
None;

A. Palanichamy,
None;

I. Sanz,
None;

J. H. Anolik,

Medimmune,

5,

UCB,

5.

  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/activated-memory-b-cell-compartment-in-rheumatoid-arthritis-impact-of-b-cell-depletion-therapy/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.