Transcriptomic analysis of pathways associated with alpha(v) integrin-related non-canonical autophagy in human B cells
Sagadiev, S.; Muir, V.; Suchland, E.; MEITLIS, I.; Giltiay, N.; Tam, J.; Garner, E. C.; Wivagg, C.; Shows, D.; James, R.; Lacy-Hulbert, A.; Acharya, M.
Show abstract
Autophagy proteins have been linked with development of immune-mediated diseases including lupus, but the mechanisms for this are unclear. We have previously shown that non-canonical autophagy induced by v-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 non-canonical autophagy in B cells, we used CRISPR-mediated knockdown of autophagy genes. Integrating data from primary B cells and knockout cells we found that v-integrin-related non-canonical autophagy limits activation of specific pathways while promoting others. These data provide new mechanistic links for autophagy and immune dysregulation in diseases such as lupus.
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