Transcriptomic analysis of pathways associated with alpha(v) integrin-dependent autophagy in human B cells

Autophagy proteins have been linked with development of immune-mediated diseases including lupus, but the mechanisms for this are unclear due to complex roles of these proteins in multiple immune cell types. We have previously shown that a form of non-canonical autophagy induced by av-integrins regulates B cell activation by viral and self-antigens, in mice. Here we investigated the involvement of this pathway in B cells from human tissue. Our data revealed that autophagy is specifically induced in germinal-center and memory B cell sub-populations from human tonsil and spleen. Transcriptomic analysis showed that induction of autophagy is related to unique aspects of activated B cells such as mitochondrial metabolism. To understand the function of ITGAV/av integrin-dependent autophagy in human B cells, we used CRISPR-mediated knockdown of autophagy genes. Integrating data from primary B cells and knockout cells we found that -dependent autophagy limits activation of specific pathways related to B cell responses, while promoting others. These data provide new mechanistic links for autophagy and B cell-mediated immune dysregulation in diseases such as lupus. Sorted tonsil B cell subsets with and without stimulation subjected to RNAseq, cell lines with CRISPR of autophagy genes or ITGAV gene subjected to RNA seq