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CD23 and CD21 function as adhesion molecules in homotypic aggregation of human B lymphocytes
P Björck1, C Elenström-Magnusson, A Rosén
1Department of Immunology, Stockholm University, Sweden.
Insights
Antibodies targeting CD23 and LFA-1 inhibit homotypic B cell aggregation. This suggests CD23/CD21 and LFA-1/ICAM-1 pathways are key to B cell clumping.
Area of Science:
- Immunology
- Cell Biology
Background:
- Homotypic B cell aggregation is crucial for immune responses.
- Interleukin-4 and CD40 monoclonal antibodies (mAb) previously identified as potentiators of B cell aggregation dependent on LFA-1.
Purpose of the Study:
- To investigate the role of CD23 and CD21 in homotypic B cell aggregation.
- To identify specific epitopes and molecular interactions involved in B cell aggregation.
Main Methods:
- Utilized monoclonal antibodies (mAb) against CD23, CD21, and LFA-1 to study their effects on B cell aggregation.
- Tested inhibition and enhancement of aggregation by various antibodies and IgE.
- Investigated the role of specific CD23 epitopes and CD21 ligands.
Main Results:
- CD23 mAb inhibited B cell aggregation, similar to LFA-1 antibodies.
- Inhibition by CD23 mAb was epitope-specific (MHM6), while other epitopes and IgE had minimal effects.
- One anti-CD21 antibody (BU32) inhibited aggregation, while another (THB5) did not.
- Combined LFA-1 and CD23 mAb often completely inhibited aggregation.
Conclusions:
- LFA-1/ICAM-1 and CD23/CD21 interactions are the primary mediators of homotypic human B cell aggregation.
- Specific epitopes on CD23 and ligands for CD23 (CD21) play critical roles in this process.
Abstract:
We have previously found that interleukin-4 and CD40 monoclonal antibodies (mAb) are strong potentiators of homotypic B cell aggregation which is dependent on LFA-1. We show here that CD23 mAb were also able to inhibit aggregation to a similar extent as LFA-1 antibodies. This inhibition was restricted to the MHM6 epitope of CD23 and antibodies to other epitopes [Epstein-Barr virus (EBV) CS-1, EBV CS-2, EBV CS-5 and mAb 25] or occupation of the Fc-binding site by IgE had no or a slightly enhancing effect on aggregation. When testing two antibodies to CD21, the recently defined ligand for CD23, one of these (BU32) was found to be inhibitory whereas the other (THB5) had no effect. By combining antibodies to LFA-1 and CD23, aggregation was often completely inhibited. These data suggest that LFA-1/ICAM-1 and CD23/CD21 are the major molecules involved in homotypic aggregation of human B cells.