| First Author | Khass M | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 906649 | PubMed ID | 36189270 |
| Mgi Jnum | J:334198 | Mgi Id | MGI:7344747 |
| Doi | 10.3389/fimmu.2022.906649 | Citation | Khass M, et al. (2022) Loss of early B cell protein lambda5 decreases bone mass and accelerates skeletal aging. Front Immunol 13:906649 |
| abstractText | The early B cell protein lambda5 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 lambda5 and/or B cells on bone acquisition over time, we developed a panel of JH (-/-) , lambda5(-/-), JH (-/-) lambda5(-/-), 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 JH (-/-) mice was similar to WT mice at all ages. In contrast, at six months of age and thereafter, lambda5(-/-) and JH (-/-) lambda5(-/-) mice demonstrated a severe decrease in trabecular bone mass. Surprisingly, bone mass in six-month-old lambda5(-/-) and JH (-/-) lambda5(-/-) 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 JH (-/-) lambda5(-/-) mice were generally comparable to WT. However, JH (-/-) lambda5(-/-) mice showed a significant decrease in cortical BV/TV at six- and twelve months of age. To examine the contribution of lambda5 and B cells to postnatal bone synthesis, we separately transplanted whole bone marrow cells from JH (-/-) lambda5(-/-) and WT mice into irradiated JH (-/-) lambda5(-/-) and WT recipients. WT recipients of JH (-/-) lambda5(-/-) marrow cells failed to show acquisition of trabecular bone mass, whereas transplanting WT marrow cells into JH (-/-) lambda5(-/-) recipients led to the recovery of trabecular bone mass. Transfer of WT marrow cells into JH (-/-) lambda5(-/-) mice promoted synthesis of new cortical and trabecular bone. Our findings indicate that lambda5 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 lambda5 and B cells in JH (-/-) lambda5(-/-) mice leads to delayed acquisition of cortical bone during postnatal development. Dissecting the mechanism(s) by which lambda5 regulates bone homeostasis may provide new avenues for the treatment of age-related loss of bone mass and osteoporosis. |
