Labrie, Joseph E. IIISah, Alex P.Allman, David M.Cancro, Michael P.Gerstein, Rachel M.2022-08-232022-08-232004-08-182008-10-31<p>J Exp Med. 2004 Aug 16;200(4):411-23. <a href="http://dx.doi.org/10.1084/jem.20040845">Link to article on publisher's site</a></p>0022-1007 (Print)10.1084/jem.2004084515314072https://hdl.handle.net/20.500.14038/38150During aging, adaptive immunity is severely compromised, due in part to decreased production of B lymphocytes and loss of immunoglobulin (Ig) diversity. However, the molecular mechanisms that underlie age-associated diminished B cell production remain unclear. Using in vivo labeling, we find that this reduction in marrow pre-B cells reflects increased attrition during passage from the pro-B to pre-B cell pool. Analyses of reciprocal bone marrow chimeras reveal that the magnitude and production rates of pre-B cells are controlled primarily by microenvironmental factors, rather than intrinsic events. To understand changes in pro-B cells that could diminish production of pre-B cells, we evaluated rag2 expression and V(D)J recombinase activity in pro-B cells at the single cell level. The percentage of pro-B cells that express rag2 is reduced in aged mice and is correlated with both a loss of V(D)J recombinase activity in pro-B cells and reduced numbers of pre-B cells. Reciprocal bone marrow chimeras revealed that the aged microenvironment also determines rag2 expression and recombinase activity in pro-B cells. Together, these observations suggest that extrinsic factors in the bone marrow that decline with age are largely responsible for less efficient V(D)J recombination in pro-B cells and diminished progression to the pre-B cell stage.en-USAgingAnimalsB-LymphocytesBone MarrowBromodeoxyuridineDNA-Binding ProteinsFlow CytometryGene Expression RegulationImmunity, CellularMiceMice, Inbred StrainsTime FactorsVDJ RecombinasesImmunology and Infectious DiseaseBone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged miceJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2032&context=oapubs&unstamped=1https://escholarship.umassmed.edu/oapubs/1033659218oapubs/1033