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Native soluble CD5 delivers a costimulatory signal to resting human B lymphocytes
1Division of Physiology-Immunology, Medical School of the Vrije Universiteit Brussel, Belgium.
Insights
The CD5 protein interacts with CD72 on B cells, enhancing their activation and proliferation. This CD5/CD72 signaling provides a costimulatory signal, suggesting a role in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- The CD5 protein is known to bind the B cell antigen CD72.
- Functional evidence for the CD5-CD72 interaction's role in B cell activation was previously lacking.
Purpose of the Study:
- To investigate the functional role of CD5 in human B cell activation through its interaction with CD72.
- To determine if CD5/CD72 signaling provides a costimulatory signal for B cells.
Main Methods:
- Utilized soluble native CD5 and anti-CD72 monoclonal antibodies (JT3, WL225).
- Assessed thymidine incorporation in human B cells stimulated with anti-sIgM, anti-CD40, or IL-4, with or without CD5 or anti-CD72 antibodies.
- Confirmed specificity of CD5 binding to CD72 using soluble recombinant CD72.
Main Results:
- CD5 and anti-CD72 antibodies significantly increased thymidine uptake in anti-sIgM activated B cells.
- CD5 binding to CD72 was specific and effective at low concentrations.
- Anti-CD72 antibodies, but not soluble CD5, provided costimulation with anti-CD40 or IL-4.
Conclusions:
- The CD5/CD72 interaction delivers a costimulatory signal to human B cells.
- This signaling pathway may play a role in physiological humoral immune responses.
Abstract:
Recently, we reported that the CD5 protein can bind to the B cell antigen CD72. So far, no functional evidence has been given for this interaction. We used soluble native CD5 and two anti-CD72 monoclonal antibodies, JT3 and WL225, produced and characterized in our laboratory in order to investigate the role of CD5 in B cell activation. Neither the CD5 nor the antibodies induced thymidine incorporation when added to resting human B cells, but they produced a two- to five-fold increase in thymidine uptake of B cells activated using immobilized anti-sIgM mAb when compared to the cultures stimulated by anti-sIgM mAb alone. The CD5 protein was effective at concentrations as low as 0.15 microM and its effect could be abolished by preincubation with soluble recombinant CD72 but not by preincubation with control proteins, indicating the specificity of the binding. The two antibodies but not the soluble CD5 produced a costimulatory effect when B cells were stimulated with suboptimal concentrations of anti-CD40 mAb or IL-4. Altogether these data suggest that a costimulatory signal can be delivered to human B cells by CD5/CD72 interaction. The possible role of CD5/CD72 signalling in physiologic humoral responses is discussed here.