Development and function of murine B cells lacking RANK.
RANKL-RANK signaling regulates numerous physiologic processes such as bone remodeling, lymph node organogenesis, central thermoregulation, and formation of a lactating mammary gland in pregnancy. Recently, a receptor activator of NF-κB ligand (RANKL)-blocking Ab has been approved for human use in potentially millions of osteoporosis and cancer patients. However, germline deficiencies in RANKL or receptor activator of NF-κB (RANK) also lead to strong B cell defects in mice and human patients, suggesting that RANKL-RANK inhibition could interfere with B cell physiology and thereby trigger immunologic side-effects. To address this key question--that is, whether RANKL-RANK signaling affects B cell physiology directly or the observed defects are secondary because of the severe osteopetrosis--we generated B cell-specific RANK knockout mice. We show that B cells deficient for RANK undergo normal development and do not show any obvious defects in Ab secretion, class switch recombination, or somatic hypermutation. Our data indicate that ablation of the RANKL-RANK pathway has no direct adverse effect on B cell physiology.
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
Thomas
T
Perlot
Josef M
JM
Penninger
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D051379:Mice; D018345:Mice, Knockout; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction; D027041:Somatic Hypermutation, Immunoglobulin
D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse