Associate Professor University of Kentucky, United States
Disclosure(s):
Ritu Chakravarti, PhD: No financial relationships to disclose
Introduction/Rationale: Dysregulated B-cell function is a central pathogenic contributor to rheumatoid arthritis (RA). Although B cells originate in the bone marrow and undergo maturation within the spleen, the manner by which defects in splenic B-cell differentiation influence RA susceptibility and severity remains inadequately defined. We have previously reported that 14-3-3ζ knockout (KO) rats exhibit marked susceptibility to experimental RA. To interrogate the role of 14-3-3ζ in humoral immune regulation, we examined its role in immune homeostasis.
Methods: We performed an integrated analysis of immune homeostasis in 14-3-3ζKO animals using single-cell transcriptomics, multiparametric flow cytometry, and immunohistochemistry across primary and secondary lymphoid organs.
Results: Our results showed that loss of 14-3-3ζ produced a lymphocyte imbalance characterized by selective expansion of defined B- and T-cell subsets and profound disruption of splenic microarchitecture. Notably, follicular development—with prominent defects in the perifollicular zone—was severely compromised in KO spleens.
Conclusion: These data indicate that 14-3-3ζ is a critical regulator of B-cell differentiation and activation and that its deficiency perturbs the cellular milieu underlying autoimmune predisposition. Further studies are underway to map the molecular pathways that connect these cellular alterations to RA pathogenesis.
