%0 Journal Article %A Aleksandra Bilska %A Monika Kusio-Kobiałka %A Paweł S. Krawczyk %A Olga Gewartowska %A Bartosz Tarkowski %A Kamil Kobyłecki %A Jakub Gruchota %A Ewa Borsuk %A Andrzej Dziembowski %A Seweryn Mroczek %T B cell humoral response and differentiation is regulated by the non-canonical poly(A) polymerase TENT5C %D 2019 %R 10.1101/686683 %J bioRxiv %P 686683 %X TENT5C is a non-canonical cytoplasmic poly(A) polymerase (ncPAP) upregulated in activated B cells and suppressing their proliferation. Herein we measured the global distribution of poly(A) tail lengths in responsive B cells using a modified Nanopore direct RNA-sequencing approach and revealed that TENT5C polyadenylates immunoglobulin mRNAs regulating their steady-state levels. Consequently, TENT5C deficient B cells secrete less antibodies and KO mice have diminished gamma globulin concentrations despite the increased number of CD138high plasma cells as a consequence of accelerated differentiation. TENT5C is explicitly upregulated in differentiating plasma cells by innate signaling. Importantly, TENT5C deficiency in B lymphocytes impairs the capacity of the secretory pathway through the reduction of ER volume and downregulation of unfolded protein response.Our findings define the role of the TENT5C enzyme in B cell physiology and discover the first ncPAP engaged in the regulation of immunoglobulin mRNA poly(A) tails, thus serving as a regulator of humoral immunity. %U https://www.biorxiv.org/content/biorxiv/early/2019/07/09/686683.full.pdf