CD22L Conjugation to Insulin Attenuates Insulin-Specific B Cell Activation.

ABSTRACT: Pancreatic islet-reactive B lymphocytes promote Type 1 diabetes (T1D) by presenting an antigen to islet-destructive T cells. Teplizumab, an anti-CD3 monoclonal, delays T1D onset in patients at risk, but additional therapies are needed to prevent the disease entirely. Therefore, bifunctional molecules were designed to selectively inhibit T1D-promoting anti-insulin B cells by conjugating a ligand for the B cell inhibitory receptor CD22 (i.e., CD22L) to insulin, which permit these molecules to concomitantly bind to anti-insulin B cell receptors (BCRs) and CD22. Two prototypes were synthesized: 2:2 insulin-CD22L conjugate on a 4-arm PEG backbone, and 1:1 insulin-CD22L direct conjugate. Transgenic mice (125Tg^SD) expressing anti-insulin BCRs provided cells for in vitro testing. Cells

SUBMITTER: Apley KD 

PROVIDER: S-EPMC11034786 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature