Defining a functionally distinct, lineage dependent B1 cell population in Nippostrongylus brasiliensis infection

Abstract

Abstract Nippostrongylus brasiliensis (Nb) is the strongest natural inducer of IgE. Despite this fact, asthma rates have an inverse correlation in countries endemic with parasitic infection. Our lab as well as others have sought to explain this phenomenon with little success. The mechanism behind this relationship is complicated by the fact that two different lineages of B cells, that are difficult to distinguish, are capable of making IgE. These B cell populations, B1 cells and B2 cells, have been classically separated using cell surface markers, but our data shows that these markers do not truly define these populations. Our lab has previously shown that IgE, using classical separation of these B cells, have functional differences in a Nb response. Current work shows that these populations have increased plasticity in a location dependent manner. High dimensional flow cytometry analysis of B cell populations, before and after Nb infection, illustrate this phenomenon. Using a lineage specific mouse model, reconstituted with fetal derived B cells that secrete FLAG-tagged IgE, we demonstrate that fetal derived B1 cells are not responsible for IgE production in Nb infection. However, hematopoietic cells expressing B1 markers are a significant source for this IgE. These data support a functionally distinct B cell population that is hematopoietic derived and has been previously classified as B1 cells. Supported by grants from the NIH-NIAID (R56 AI139658-01AI)