Caveolin-1 is dispensable for early lymphoid development, but plays a role in the maintenance of the mature splenic microenvironment

Abstract

Abstract Objective Caveolin-1 (CAV1) is known for its role as both a tumor suppressor and an oncogene, harboring a highly context-dependent role within a myriad of malignancies and cell types. In an immunological context, dysregulation of CAV1 expression has been shown to alter immunological signaling functions and suggests a pivotal role for CAV1 in the facilitation of proper immune responses. Nonetheless, it is still unknown how Cav1-deficiency and heterozygosity would impact the development and composition of lymphoid organs in mice. Herein, we investigated the impacts of Cav1-dysregulation on the lymphoid organs in young (12 weeks) and aged (36 weeks) Cav1 +/+, Cav1 +/−, and Cav1 −/− mice. Results We observed that only Cav1-deficiency is associated with persistent splenomegaly at all timepoints. Furthermore, no differences in overall body weight were detected (and without sexual dimorphisms). Both aged Cav1 +/− and Cav1 −/− mice present with decreased CD19+CD22+ B cells and secondary-follicle atrophy, specifically in the spleen, compared with wild-type controls and irrespective of splenomegaly status. Consequently, the demonstrated effects on B cell homeostasis and secondary follicle characteristics prompted our investigation into follicle-derived human B-cell lymphomas. Our investigation points toward CAV1 as a dysregulated protein in follicle-derived B-cell malignancies without harboring a differential expression between more aggressive and indolent hematological malignancies.

Keywords

• Caveolin-1
• Immunophenotype
• Spleen
• B cell