Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca channel function.

TCR stimulation triggers Ca signals that are critical for T cell function and immunity. Several pore-forming α and auxiliary β subunits of voltage-gated Ca channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca signaling in T cells is controversial. We here identify Caβ1, encoded by Cacnb1, as a regulator of T cell function. Cacnb1 deletion enhances apoptosis and impairs the clonal expansion of T cells after lymphocytic choriomeningitis virus (LCMV) infection. By contrast, Cacnb1 is dispensable for T cell proliferation, cytokine production and Ca signaling. Using patch clamp electrophysiology and Ca recordings, we are unable to detect voltage-gated Ca currents or Ca influx in human and mouse T cells upon depolarization with or without prior TCR stimulation. mRNAs of several VGCC α1 subunits are detectable in human (Ca3.3, Ca3.2) and mouse (Ca2.1) T cells, but they lack transcription of many 5' exons, likely resulting in N-terminally truncated and non-functional proteins. Our findings demonstrate that although Caβ1 regulates T cell function, these effects are independent of VGCC channel activity.