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Updated: Aug 8, 2026

Murine Model of CD40-activation of B cells
Published on: March 6, 2010
Regulation of resting and cycling human B lymphocytes via surface IgM and the accessory molecules interleukin-4, CD23
J Gordon1, M J Millsum, L Flores-Romo
1Department of Immunology, University of Birmingham, U.K.
Insights
A new monoclonal antibody targeting the mu chain effectively stimulates B lymphocytes. Immobilization and co-stimulants like IL-4 enhance B cell responses and IgM secretion in both resting and cycling cells.
Area of Science:
- Immunology
- Cell Biology
- B lymphocyte activation
Background:
- B lymphocytes require specific signals for activation and proliferation.
- Monoclonal antibodies targeting B cell surface molecules are crucial tools in immunology research.
- Understanding B cell activation pathways is key to developing immunotherapies.
Purpose of the Study:
- To evaluate a novel monoclonal anti-mu chain antibody for its ability to initiate and maintain B lymphocyte stimulation.
- To compare the efficacy of soluble versus immobilized anti-mu antibody in activating resting and cycling B cells.
- To investigate the role of co-stimulatory signals, including IL-4 and CD40 antibodies, in modulating B cell responses.
Main Methods:
- Utilized resting and cycling B lymphocyte populations.
- Applied soluble and immobilized monoclonal anti-mu chain antibodies.
- Incorporated co-stimulatory signals: phorbol ester, IL-4, and CD40 antibody (G28-5).
- Measured B cell stimulation magnitude and duration, IgM secretion, and soluble CD23 release.
Main Results:
- Immobilized anti-mu enhanced resting B cell responses, reducing co-factor requirements.
- IL-4 alone unexpectedly reduced background stimulation with high-dose immobilized anti-mu.
- Both soluble and immobilized anti-mu sustained cycling B cell stimulation, prolonged by IL-4 and/or G28-5.
- A correlation was observed between IL-4-induced stimulation, CD23 release, and augmentation by CD23 antibody (MHM6).
- IL-4 and G28-5 induced IgM secretion, differentially modulated by anti-mu in resting and cycling B cells.
Conclusions:
- The novel monoclonal anti-mu antibody is potent in initiating and maintaining B lymphocyte stimulation.
- Co-immobilization and co-stimulation significantly enhance B cell activation and IgM production.
- IL-4 plays a critical role in modulating B cell responses, particularly in conjunction with anti-mu and CD40 signaling.
Abstract:
Experiments were designed in order to compare directly the ability of a new and potent monoclonal anti-mu chain antibody to initiate or maintain stimulation in resting and cycling B lymphocytes, respectively. Resting B cells could be stimulated by soluble anti-mu only in the presence of additional signals; these could be supplied by a high dose of phorbol ester or a combination of interleukin-4 (IL-4) and the CD40 antibody, G28-5. Immobilization of anti-mu not only increased the magnitude of the resting B-cell response but also diminished the co-factor requirements. The 'background' stimulation obtained when using a high concentration of immobilized anti-mu was unexpectedly reduced in the presence of IL-4 alone. The duration, but not the magnitude, of the IL-4 signal required for promoting optimal responses varied with the co-stimulation applied. Importantly, the threshold concentrations of soluble anti-mu needed to trigger the resting B cells were reduced upon the addition of each co-stimulant. With actively cycling B cells, both soluble and immobilized anti-mu were now capable of sustaining stimulation which could be prolonged on the addition of IL-4 and/or G28-5. In both resting and cycling populations, a strong correlation was noted between the magnitude of stimulation elicited when IL-4 was present and the release of the soluble CD23 molecule. Moreover, IL-4-promoted, but not other, stimulations could be augmented up to 10-fold by the inclusion of the CD23 antibody MHM6. Both the resting and cycling B-cell populations were found to secrete IgM in direct response to IL-4 and G28-5; this factor-driven production of IgM was differentially modulated by soluble and immobilized anti-mu in the two populations.
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