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Apoptosis and antigen affinity limit effector cell differentiation of a single naïve B cell

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Science  13 Feb 2015:
Vol. 347, Issue 6223, pp. 784-787
DOI: 10.1126/science.aaa1342

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For a single B cell, many roads to take

To successfully fight a pathogen, immunological B cells must wage a multipronged attack: They can differentiate into antibody-secreting plasma cells or become T cell–helping germinal center cells, or even long-lived memory cells. But can a single B cell acquire all of these different fates? To find out, Taylor et al. tracked the responses of single B cells in mice. Although some B cells acquired only one fate, others differentiated into all three. The authors linked the ability of B cells to differentiate into multiple subsets to their ability to proliferate and resist cell death, and the affinity of their antigen receptor.

Science, this issue p. 784

Abstract

When exposed to antigens, naïve B cells differentiate into different types of effector cells: antibody-producing plasma cells, germinal center cells, or memory cells. Whether an individual naïve B cell can produce all of these different cell fates remains unclear. Using a limiting dilution approach, we found that many individual naïve B cells produced only one type of effector cell subset, whereas others produced all subsets. The capacity to differentiate into multiple subsets was a characteristic of clonal populations that divided many times and resisted apoptosis, but was independent of isotype switching. Antigen receptor affinity also influenced effector cell differentiation. These findings suggest that diverse effector cell types arise in the primary immune response as a result of heterogeneity in responses by individual naïve B cells.

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