Loss of early B cell protein λ5 decreases bone mass and accelerates skeletal aging

The early B cell protein λ5 is an essential component of the surrogate light chain and the preB cell receptor (preBCR), which is critical for optimal B cell development. To investigate the effect of λ5 and/or B cells on bone acquisition over time, we developed a panel of J , λ5^-/-, J λ5^-/-, and wild-type (WT) BALB/c mice and then studied postnatal bone development and aging in these mice at one, six, twelve, and twenty-two months of age. The trabecular bone volume over total volume (BV/TV) in J mice was similar to WT mice at all ages. In contrast, at six months of age and thereafter, λ5^-/- and J λ5^-/- mice demonstrated a severe decrease in trabecular bone mass. Surprisingly, bone mass in six-month-old λ5^-/- and J λ5^-/- mice was similar to or even lower than in aged (twenty-two-months) WT mice, suggesting accelerated skeletal aging. The postnatal development and the acquisition of cortical bone mass in J λ5^-/- mice were generally comparable to WT. However, J λ5^-/- mice showed a significant decrease in cortical BV/TV at six- and twelve months of age. To examine the contribution of λ5 and B cells to postnatal bone synthesis, we separately transplanted whole bone marrow cells from J λ5^-/- and WT mice into irradiated J λ5^-/- and WT recipients. WT recipients of J λ5^-/- marrow cells failed to show acquisition of trabecular bone mass, whereas transplanting WT marrow cells into J λ5^-/- recipients led to the recovery of trabecular bone mass. Transfer of WT marrow cells into J λ5^-/- mice promoted synthesis of new cortical and trabecular bone. Our findings indicate that λ5 plays a major role in preserving bone mass during postnatal development and skeletal aging which is distinct from its role in B cell development. The absence of both λ5 and B cells in J λ5^-/- mice leads to delayed acquisition of cortical bone during postnatal development. Dissecting the mechanism(s) by which λ5 regulates bone homeostasis may provide new avenues for the treatment of age-related loss of bone mass and osteoporosis.