How B cells influence bone biology in health and disease.
It is now well established that important regulatory interactions occur between the cells in the hematopoietic, immune and skeletal systems (osteoimmunology). B lymphocytes (B cells) are responsible for the generation and production of antibodies or immunoglobulins in the body. Together with T cells these lymphocytes comprise the adaptive immune system, which allows an individual to develop specific responses to an infection and retain memory of that infection, allowing for a faster and more robust response if that same infection occurs again. In addition to this immune function, B cells have a close and multifaceted relationship with bone cells. B cells differentiate from hematopoietic stem cells (HSCs) in supportive niches found on endosteal bone surfaces. Cells in the osteoblast lineage support HSC and B cell differentiation in these niches. B cell differentiation is regulated, at least in part, by a series of transcription factors that function in a temporal manner. While these transcription factors are required for B cell differentiation, their loss causes profound changes in the bone phenotype. This is due, in part, to the close relationship between macrophage/osteoclast and B cell differentiation. Cross talk between B cells and bone cells is reciprocal with defects in the RANKL-RANK, OPG signaling axis resulting in altered bone phenotypes. While the role of B cells during normal bone remodeling appears minimal, activated B cells play an important role in many inflammatory diseases with associated bony changes. This review examines the relationship between B cells and bone cells and how that relationship affects the skeleton and hematopoiesis during health and disease.
Horowitz
Mark C
MC
Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA. mark.horowitz@yale.edu
Fretz
Jackie A
JA
Lorenzo
Joseph A
JA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001851:Bone Diseases, Metabolic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D004967:Estrogens / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000502:physiology; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D004967:Estrogens; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D014157:Transcription Factors