# Disrupting CD22-cis-ligand interactions ameliorates type 1 diabetes and graft rejection by expanding regulatory B cells

## TL;DR

Blocking CD22 interactions in B cells expands regulatory cells that help prevent diabetes and transplant rejection in mice.

## Contribution

A novel therapeutic strategy targeting CD22-ligand interactions to treat autoimmune and transplant-related diseases.

## Key findings

- Blocking CD22 ligand binding expands regulatory B cells in mice.
- Treatment with anti-CD22 antibody 1C5 ameliorates type 1 diabetes and graft rejection.
- CD22 ligand interaction appears to suppress TLR signaling required for Breg cell expansion.

## Abstract

CD22 is an inhibitory receptor expressed in B cells and is constitutively associated with α2,6-sialylated membrane proteins expressed on the same cell (cis-ligands). However, interaction with cis-ligands is required for the function of CD22 only in part. To address the role of ligand interaction of CD22 in immune responses, here we generated anti-CD22 antibody 1C5 that specifically inhibits ligand binding of CD22. Both Cd22−/− mice and mice treated with 1C5 show expansion of regulatory B (Breg) cells in follicular (FO) B cells, suggesting a crucial role of ligand interaction of CD22 in inhibiting the expansion of FO Breg cells. CD22 appears to recognize BCR and TLRs thereby directly or indirectly suppressing TLR signaling essential for expansion of Breg cells. Treatment of mice with 1C5 ameliorates skin graft rejection and type 1 diabetes with expansion of regulatory γδ T cells probably through expansion of Breg cells, suggesting ligand interaction of CD22 as a novel target of therapy for autoimmune diseases and graft rejection.

Autoimmune diabetes and transplant rejection arise when immune checkpoints fail to restrain inflammatory responses. This study shows that blocking CD22 binding to its natural ligands expands regulatory B cells and protective γδ T cells, suppressing type 1 diabetes and prolonging skin graft survival in mice.