Machine Learning to Quantify In Situ Humoral Selection in Human Lupus Tubulointerstitial Inflammation.

ABSTRACT: In human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation (SHM) and selection increase affinity for vimentin. Indeed, germline reversion of several antibodies demonstrated that higher affinity AVAs can be selected from both low affinity B cell germline clones and even those that are strongly reactive with other autoantigens. While we demonstrated affinity maturation, enzyme-linked immunosorbent assays (ELISAs) suggested that affinity maturation might be a consequence of increasing polyreactivity or even non-specific binding. Therefore, it was unclear if there was also selection for

SUBMITTER: Kinloch AJ 

PROVIDER: S-EPMC7731665 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature