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Abstract Number: 971

B Cell ROCK1 Promotes Germinal Center Responses and Is Required for Optimal Humoral Immunity

Edd Ricker1, Danny Flores-Castro 2, Sanjay Gupta 3, Andrew Cheng 3, Yurii Chinenov 3, Tania Pannellini 2, Young-Bum Kim 4 and Alessandra Pernis 5, 1Hospital for Special Surgery, New York, NY, 2Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, 3Hospital for Special Surgery, New York, 4Beth Israel Deaconess Medical Center, Boston, MA, 51.Autoimmunity and Inflammation Program, Hospital for Special Surgery. 2.David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery. 3.Department of Medicine, Weill Cornell Medical College, Cornell University, New York

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: adaptive immunity and Cell Signaling, B cells

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Session Information

Date: Monday, November 11, 2019

Session Title: B Cell Biology & Targets In Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Rho GTPases, such as RhoA, have emerged as important regulators of lymphocyte biology owing to their ability to be rapidly activated downstream of a broad range of signals. Two of the major effectors of RhoA signaling are the Rho Kinases (ROCKs), ROCK1 and ROCK2, a pair of serine-threonine kinases that have been previously implicated in the control of cell adhesion, migration, proliferation/survival, and gene expression. Despite the fundamental reliance of T and B cells on these processes, the precise involvement of the ROCKs in lymphocyte biology is yet to be elucidated. Here, we investigate the contribution of ROCK1 to B cell development and differentiation following immunization with a T-dependent antigen.

Methods: To assess the roles of B cell ROCK1 in T cell-dependent responses, mice with B cell-specific deletions of ROCK1 (CD23-Cre.Rock1flox/flox and Cγ-Cre.Rock1flox/flox mice) were immunized with a T-dependent antigen. Rock1flox/flox mice were also immunized as a control for this study. The differentiation of germinal center (GC) B cells and plasmablast/plasma cells (PB/PCs) was monitored by FACS at various timepoints following immunization. Total and antigen-specific antibody responses were also assessed by ELISA. The molecular mechanisms employed by ROCK1 to promote B cell differentiation were further examined by FACS-sorting B cell populations from spleens of immunized mice followed by RNA-sequencing analyses.

Results: We found that ROCK1 is expressed and activated in splenic B cells. Mice with B cell-specific deletion of ROCK1 showed marked reductions in total and antigen-specific antibody responses following immunization. These decreased humoral responses corresponded with impaired formation and maintenance of antigen-specific GC B cells and PB/PCs following immunization in the ROCK1-deficient mice. Through next generation sequencing, we have furthermore identified a ROCK1-regulated transcriptional program that supports the phenotype of GC B cells.

Conclusion: Our study demonstrates that ROCK1 is activated in B cells and is required for the optimal development of mature B cell populations at baseline and for efficient GC responses following immunization. These findings thus uncover previously unknown B cell-specific roles for ROCK1 in promoting humoral responses and suggests that targeting ROCK1 activity may provide therapeutic benefit for the treatment of diseases marked by aberrant B cell responses.


Disclosure: E. Ricker, None; D. Flores-Castro, None; S. Gupta, None; A. Cheng, None; Y. Chinenov, None; T. Pannellini, None; Y. Kim, None; A. Pernis, Kadmon pharmaceutical, 2.

To cite this abstract in AMA style:

Ricker E, Flores-Castro D, Gupta S, Cheng A, Chinenov Y, Pannellini T, Kim Y, Pernis A. B Cell ROCK1 Promotes Germinal Center Responses and Is Required for Optimal Humoral Immunity [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/b-cell-rock1-promotes-germinal-center-responses-and-is-required-for-optimal-humoral-immunity/. Accessed May 26, 2022.
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