Reciprocal haematopoietic cell transfers between C57BL/6 mice differing at the lpr locus

Abstract

Reciprocal transfers of spleen and bone marrow cell suspensions have been performed between mice of the C57BL/6 (B6) genetic background, differing at the lymphoproliferation (lpr) locus. These immune system chimaeras were followed for almost one year after sublethal irradiation and cell reconstitution. In addition to the survival of the chimaeras, the major lymphoid organs (bone marrow, spleen, thymus and lymph nodes) were examined for cell numbers, percentages of membrane immunoglobulin-positive cells and responses to mitogenic stimulations with concanavalin and lipopolysaccharide. The [lpr----lpr] chimaeras were similar to untreated lpr mice. The [wild----lpr] did not develop the lpr-induced syndrome and remained similar to [wild----wild] chimaeras. Therefore, B6 wild haematopoietic stem cells could rescue sublethally irradiated B6 lpr mice from the lpr-induced autoimmune pathology. The radioresistant lpr environment alone was not sufficient to induce the lpr syndrome. It may however be required for its development since [lpr----wild] chimaeras displayed a profound aplasia of their lymphoid organs, together with a normal cellularity of their bone marrow. In contrast to chimaeras constructed with MRL mice, the [lpr----wild] B6 chimaeras did not die following the lpr haematopoietic stem cell transfer. Therefore, the lymphoid aplasia of [lpr----wild] radiation chimaeras does not result from an lpr graft-versus-host-like syndrome. More likely is that a normal, non-lpr, haematopoietic environment may not allow the differentiation of the lpr haematopoietic stem cells into the lymphoid lineages.