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International Immunology, Vol 9, 239-248, Copyright © 1997 by Oxford University Press


ARTICLES

A new multivalent B cell activation model--anti-IgD bound to Fc gamma RI: properties and comparison with CD40L-mediated activation

S Cho and DH Conrad
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298, USA.

CHO cells permanently transfected with mouse Fc gamma RI alpha chain were prepared and used as a model to polyclonally activate murine B cells. The transfected CHO cells were treated with mitomycin C and placed into culture with varying quantities of anti-IgD. Using this model, murine splenic B cells (from BALB/c or C57Bl/6) were activated by mouse IgG2a-anti-IgD (10.4.22 or AF3.33) in a manner that is analogous to the activation of B cells seen with highly polyvalent anti- IgD (H delta(a)/1) prepared by chemical cross-linking to dextran. Efficient B cell activation was seen with nanogram quantities of anti- IgD. In the presence of IL-4 and IL-5, IgG1 production levels were equivalent to or better than seen when stimulation was with H delta(a)/1-dextran; however, IgE induction was not seen in either situation. The Ig production capacity was compared to that seen when B cells were activated with CD40L, using either CD40L-transfected CHO or a soluble CD40L construct. In the presence of IL-4 and IL-5, once a critical threshold of B cells was present, IgE and to a lesser extent IgG1 production was inversely proportional to B cell number when CD40L was the activating agent. In contrast, with Fc gamma RI-anti-IgD, IgM and IgG1 production was directly proportional to B cell number, while IgE production was never seen. Finally, when B cells were co-activated with immobilized anti-IgD and CD40L simultaneously, the IgE production from B cells induced by CD40L was strongly inhibited, while IgG1 and IgM production were not affected. Since B cell co-activation via sIg and CD40L would be a common scenario in secondary follicles, this inhibition of IgE production may be one of the reasons why serum IgE levels are much below IgG in normal immune situations.
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