Persistence of lpr/lpr-derived lgG2a secreting B cells in normal → lpr/lpr adult radiation chimeras or lpr/lpr → normal kidney capsule chimeras

Abstract

Lethally irradiated MRL/lpr mice reconstituted with bone marrow stem cells from a normal mouse strain develop a state of split hematopoietic chimerism; erythrocytes, granulocytes, and macrophages are derived from the normal stem cell inoculum while the peripheral T lymphocytes are derived from radioresistant lpr host cells. Moreover, these mice have normal levels of serum IgM and IgG2a produced by radioresistant host B cells, even though they have relatively few sIgM + B cells. In order to better understand the differentiation and regulation of B cells present in these chimeric mice, the current study was undertaken to localize and to assess the functional capacity of the lpr B cells producing the serum antibodies. Surface IgG2a + cells could not be found in the spleen or lymph nodes of these mice, but large lymphocytes containing cytoplasmic IgG2 of host ( lpr) allotype could be readily detected, even though they constituted less than 1% of the total spleen population. The host-derived serum IgG2 and IgG2 + cells were even present in the spleens of “leaky” mice that had relatively normal numbers of donor-derived sIgM + B cells. These lpr B cells secreted IgG2a antibody that bound ssDNA, but they could not respond to immunization with SRBC. These results indicate that the lpr-derived radioresistant B cells have a limited capacity for proliferation and are already committed to the memory lineage. The presence of similar B cells in normal mice transplanted with neonatal lpr/lpr spleen fragments suggests that lpr/lpr B cell development is inherently abnormal.