To address this, Taylor et al. used a limiting dilution approach to track the response of individual antigen-reactive naive B cells during immunization with the protein allophycocyanin. Based on calculations from preliminary experiments, the authors transferred a certain number of polyclonal naive B cells into recipient mice that were subsequently immunized with allophycocyanin in complete Freund's adjuvant, with the expectation that less than one donor-derived allophycocyanin-responsive naive B cell would survive in each recipient. At 7 days following immunization, donor-derived allophycocyanin-responsive B cells could be detected in 19% of the recipient mice and, based on the Poisson distribution, more than 91% of these populations arose from a single naive B cell.
The populations that differentiated from individual naive B cells were highly heterogeneous in terms of overall size and composition. Single naive B cells produced between four and 957 progeny (with a mean of 16) and although 44% of the clonal populations comprised only one effector cell type (namely, plasma cells, GC B cells, memory B cells or undifferentiated activated precursors), many populations contained two or three effector cell types, and a few populations contained all four subsets. Larger clonal populations were more likely to contain multiple effector cell types but surprisingly, population size did not correlate with an increased rate of cell division. Furthermore, populations containing all four effector cell subsets exceeded their expected size, whereas the populations with only one effector cell type had a lower than expected median size. This suggested that resistance to cell death may be linked to the multipotentiality of the progeny of a single naive B cell.
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