Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca2+ channel function

TCR stimulation triggers Ca2+ signals that are critical for T cell function and immunity. Several pore-forming alpha and auxiliary beta subunits of voltage-gated Ca2+ channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca2+ signaling in T cells is controversial. We here identify Ca-V beta 1, 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 Ca2+ signaling. Using patch clamp electrophysiology and Ca2+ recordings, we are unable to detect voltage-gated Ca2+ currents or Ca2+ influx in human and mouse T cells upon depolarization with or without prior TCR stimulation. mRNAs of several VGCC alpha 1 subunits are detectable in human (Ca(V)3.3, Ca(V)3.2) and mouse (Ca(V)2.1) 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 Ca-V beta 1 regulates T cell function, these effects are independent of VGCC channel activity. The function of voltage-gated calcium channels in T cells is not well understood and controversial. Here the authors report that a regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.

Automated summary

The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.