Asymmetric Segregation of Polarized Antigen on B Cell Division Shapes Presentation Capacity

Antigen Polarity in B Cell Differentiation Communication received through cell contact is critical for the differentiation of specialized effector cell populations during the immune response. For example, B lymphocytes acquire antigen that they present to helper T lymphocytes. T lymphocytes, in turn, provide key differentiation signals to B lymphocytes. In order to learn more about this process, Thaunat et al. (p. 475; see the Perspective by Dustin and Meyer-Hermann) used multiphoton microscopy and imaging flow cytometry to visualize the localization of antigen in B lymphocytes during an immune response. Antigen acquired by B lymphocytes exhibited a polarized distribution that was sustained over several rounds of cell division. This produced a population of activated B lymphocytes that contained very low levels of antigen. Daughter cells that received more antigen were better able to stimulate T cells. Because cues received through T lymphocyte interactions are likely to influence B lymphocyte fate decisions, unequal distribution of antigen in dividing B lymphocytes may influence their differentiation. Antigen distribution across activated B cells influences B-T lymphocyte interactions. During the activation of humoral immune responses, B cells acquire antigen for subsequent presentation to cognate T cells. Here we show that after mouse B cells accumulate antigen, it is maintained in a polarized distribution for extended periods in vivo. Using high-throughput imaging flow cytometry, we observed that this polarization is preserved during B cell division, promoting asymmetric antigen segregation among progeny. Antigen inheritance correlates with the ability of progeny to activate T cells: Daughter cells receiving larger antigen stores exhibit a prolonged capacity to present antigen, which renders them more effective in competing for T cell help. The generation of progeny with differential capacities for antigen presentation may have implications for somatic hypermutation and class switching during affinity maturation and as B cells commit to effector cell fates.

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