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.

doi:10.1101/2021.08.02.452710

bioRxiv · 10.1101/2021.08.02.452710

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.

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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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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.. 2021-08-02. Transcriptomic analysis of pathways associated with alpha(v) integrin-related non-canonical autophagy in human B cells. https://doi.org/10.1101/2021.08.02.452710

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