Interactions between IL-4, anti-CD40, and anti-immunoglobulin as activators of locomotion of human B cells.

The locomotor properties of small, surface IgM+ and surface IgD+ B cells from the human tonsil were studied using polarization assays and collagen gel invasion assays. These cells gave poor locomotor responses when freshly isolated from the tonsil; but 30 to 40% of the cells polarized and invaded collagen gels after overnight culture in IL-4 or anti-CD40. IL-13 had a similar but weaker effect. Culture with anti-CD40 and IL-4 together gave a higher proportion of polarized cells than either alone, and culture in anti-CD40, IL-4, and anti-IgM gave a still higher proportion (> 60% of B cells polarized). Polarization increased gradually, during hours of culture, unlike the typical rapid response to chemoattractants. We also studied the immediate (< 30 min) effects of chemoattractants on B cell polarization. B cells cultured overnight then washed, but not B cells fresh from the tonsil, polarized immediately in response to anti-CD40. Similar responses to anti-IgM and anti-IgD, both pre- and postculture were also observed, but the response of cultured cells was stronger. IL-4-cultured B cells invaded collagen gels incorporating anti-IgM, anti-IgD, or anti-CD40 in higher numbers than control gels. Most of the invading cells were surface IgM+. These results suggest that locomotor activation in B cells requires two steps. The capacity for locomotion is growth-related and is first activated by IL-4 or by anti-CD40, enhanced by the presence of anti-IgM. Following activation, the cells respond rapidly to chemoattractants such as anti-Ig or anti-CD40.