V region dependent selection of persistent resting peripheral B cells in normal mice.

In this study, we compare the VH gene family repertoire of persistent long-lived splenic B cells with that of the whole splenic B cell compartment. Persistent long-lived B cells were obtained by two independent strategies. Firstly, we studied cells that persist in the peripheral pools with or without cell division. We have transferred mature lipopolysaccharide (LPS)-reactive splenic B cells into LPS non-responder recipients and studied the donor population that could be recovered in host mice at differing time intervals after cell transfer. Secondly, we studied non-cycling resting long-lived B cells. These cells were obtained in normal mice after cytostatic treatment with hydroxyurea and in mice transgenic for the HSV-1 thymidine kinase gene after treatment with the anti-herpetic ganciclovir. Studying the VH gene family usage at the single level by in situ hybridization, we found that persistent B cells show an increased expression of the VHJ558 family and a diminished representation of the VH7183 family. These results demonstrate that in a normal non-immunized mouse, B cell survival and persistence in the resting state results from V region dependent selection.