Current studentsExisting staffContact us
 

Lymphoma driver mutations in the pathogenic evolution of an iconic human autoantibody

Simple item page
dc.contributor.authorSingh, M.
dc.contributor.authorJackson, K.J.L.
dc.contributor.authorWang, J.J.
dc.contributor.authorSchofield, P.
dc.contributor.authorField, M.A.
dc.contributor.authorKoppstein, D.
dc.contributor.authorPeters, T.J.
dc.contributor.authorBurnett, D.L.
dc.contributor.authorRizzetto, S.
dc.contributor.authorNevoltris, D.
dc.contributor.authorMasle-Farquhar, E.
dc.contributor.authorFaulks, M.L.
dc.contributor.authorRussell, A.
dc.contributor.authorGokal, D.
dc.contributor.authorHanioka, A.
dc.contributor.authorHorikawa, K.
dc.contributor.authorColella, A.D.
dc.contributor.authorChataway, T.K.
dc.contributor.authorBlackburn, J.
dc.contributor.authorMercer, T.R.
dc.contributor.authoret al.
dc.date.issued2020
dc.description.abstractPathogenic autoantibodies arise in many autoimmune diseases, but it is not understood how the cells making them evade immune checkpoints. Here, single-cell multi-omics analysis demonstrates a shared mechanism with lymphoid malignancy in the formation of public rheumatoid factor autoantibodies responsible for mixed cryoglobulinemic vasculitis. By combining single-cell DNA and RNA sequencing with serum antibody peptide sequencing and antibody synthesis, rare circulating B lymphocytes making pathogenic autoantibodies were found to comprise clonal trees accumulating mutations. Lymphoma driver mutations in genes regulating B cell proliferation and V(D)J mutation (CARD11, TNFAIP3, CCND3, ID3, BTG2, and KLHL6) were present in rogue B cells producing the pathogenic autoantibody. Antibody V(D)J mutations conferred pathogenicity by causing the antigen-bound autoantibodies to undergo phase transition to insoluble aggregates at lower temperatures. These results reveal a pre-neoplastic stage in human lymphomagenesis and a cascade of somatic mutations leading to an iconic pathogenic autoantibody.
dc.description.statementofresponsibilityMandeep Singh, Katherine J.L. Jackson, Jing J. Wang, Peter Schofield, Matt A. Field ... Maureen Rischmueller ... et al.
dc.identifier.citationCell, 2020; 180(5):878-894
dc.identifier.doi10.1016/j.cell.2020.01.029
dc.identifier.issn0092-8674
dc.identifier.issn1097-4172
dc.identifier.orcidRischmueller, M. [0000-0001-5057-3286]
dc.identifier.urihttp://hdl.handle.net/2440/124829
dc.language.isoen
dc.publisherElsevier
dc.rights© 2020 Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.cell.2020.01.029
dc.subjectautoantibody
dc.subjectcryoglobulinemia
dc.subjectlymphoma
dc.subjectrheumatoid factor
dc.subjectsingle cell omics
dc.subjectsomatic mutation
dc.subjectvasculitis
dc.titleLymphoma driver mutations in the pathogenic evolution of an iconic human autoantibody
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications