Early B cell protein λ5 affects skeletal homeostasis

Abstract

Abstract There are strong indications that B lineage cells play a key role in bone homeostasis. The preB cell receptor is composed of an immunoglobulin mu H chain, VpreB and immunoglobulin λ5. Young λ5 deficient mice have reduced numbers of preB cells and mature B cells, moreover; their bone appears to be normal. With time, they achieve normal numbers of mature B cells while exhibiting major bone loss. To test whether expression of λ5 is playing a critical role maintaining bone homeostasis, we evaluated bone in: mice lacking immunoglobulin JH (JH −/− λ5+/+). These mice lack both preB and mature B cells, but maintain expression of λ5 in progenitor B cells. Mice deficient in both JH and λ5 (JH −/− λ5−/−) have no preB or mature B cells, and also no λ5. Using both μCT and histologic evaluation, we compared femur and skull at six months of age in these three mutant strains to normal controls. JH −/− λ5+/+ femur and skull were similar to WT. Both JH +/+λ5−/− and JH −/− λ5−/− mice showed significant decrease in femoral trabecular bone and increased loss of skull bone. Irradiated WT mice transplanted with JH −/− λ5−/− bone marrow cells developed defective femoral and cranial bones. In contrast, JH −/−λ5−/− mice that received WT bone marrow cells recovered bone architecture. In vitro culture of bone progenitors from JH +/+λ5−/− and JH −/− λ5−/− mice showed decreased ability of bone formation. These data underscore the importance of immunoglobulin λ5 in skeletal development.