CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses.

ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell compartment responsible for the production of autoantibodies. Here, we show that T cell-specific expression of calcium/calmodulin-dependent protein kinase IV (CaMK4) leads to T follicular helper (T_fh) cells expansion in models of T-dependent immunization and autoimmunity. Mechanistically, CaMK4 controls the T_fh-specific transcription factor B cell lymphoma 6 (Bcl6) at the transcriptional level through the cAMP responsive element modulator α (CREMα). In the absence of CaMK4 in T cells, germinal center formation and humoral immunity is impaired in immunized mice, resulting in reduced anti-dsDNA titres, as well as IgG and complement kidney deposition in the lupus-prone B6.lpr

SUBMITTER: Scherlinger M 

PROVIDER: S-EPMC10825135 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature