Co-ligation of mouse complement receptors 1 and 2 with surface IgM rescues splenic B cells and WEHI-231 cells from anti-surface IgM-induced apoptosis
✍ Scribed by Yuko Kozono; Richard C. Duke; Mary S. Schleicher; V. Michael Holers
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 569 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Mouse CR2 and CR1 rescue B lymphocytes from anti-sIgM-induced apoptosis 1013
Co-ligation of mouse complement receptors 1 and 2 with surface IgM rescues splenic Bcells and
WEHI-231 cells from anti-surface IgM-induced apoptosis
Recent studies have shown that complement receptors play important roles in both T-dependent and T-independent B lymphocyte responses to low doses of antigen (Ag) in vivo. Complement activation by either the classical or alternative pathway results in the covalent binding of C3 molecules to Ag in forms that ligate complement receptors type 1 (CR1) and 2 (CR2). We hypothesized that C3-bound Ag might cross-link CR2 and/or CR1 with surface (s)IgM and alter the signal that would be transduced through sIgM by Ag binding alone. One result of the altered signal could be the rescue of B lymphocytes from apoptosis that would otherwise be induced by the binding of certain types of Ag alone. We find that co-cross-linking of mouse CR2 and CR1 with sIgM rescues both resting B cells and WEHI-231.7 cells from apoptosis induced by sIgM ligation in a fashion similar to that found using soluble mouse CD40 ligand (mCD40L). Anti-CR2KRl-rnediated rescue requires co-cross-linking of the receptors with sIgM, and has an additive effect on mCD40L-mediated apoptosis rescue. Based on these results, it is likely that the CR2/CRl-derived signal is cooperative with T cell-derived signals such as CD40L and interleukiin-4.
We and others have shown that CR2 and CR1 on mouse B lymphocytes are the products of alternatively spliced mRNA derived from the Cr2 gene [8,9]. Mouse CR1 has an additional domain at the amino terminus that adds C3band C4b-binding properties to the CR2 portion [lo, 111. Due to this structural characteristic, all mAb such as 7G6 that recognize mouse CR2 also recognize mouse CR1.