{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:34:56Z","timestamp":1777527296520,"version":"3.51.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2003,11,1]],"date-time":"2003-11-01T00:00:00Z","timestamp":1067644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mice deficient in the enzyme adenosine deaminase (ADA) have small lymphoid organs that contain reduced numbers of peripheral lymphocytes, and they are immunodeficient. We investigated B cell deficiency in ADA-deficient mice and found that B cell development in the bone marrow was normal. However, spleens were markedly smaller, their architecture was dramatically altered, and splenic B lymphocytes showed defects in proliferation and activation. ADA-deficient B cells exhibited a higher propensity to undergo B cell receptor-mediated apoptosis than their wild-type counterparts, suggesting that ADA plays a role in the survival of cells during Ag-dependent responses. In keeping with this finding, IgM production by extrafollicular plasmablast cells was higher in ADA-deficient than in wild-type mice, thus indicating that activated B cells accumulate extrafollicularly as a result of a poor or nonexistent germinal center formation. This hypothesis was subsequently confirmed by the profound loss of germinal center architecture. A comparison of levels of the ADA substrates, adenosine and 2\u2032-deoxyadenosine, as well resulting dATP levels and S-adenosylhomocysteine hydrolase inhibition in bone marrow and spleen suggested that dATP accumulation in ADA-deficient spleens may be responsible for impaired B cell development. The altered splenic environment and signaling abnormalities may concurrently contribute to a block in B cell Ag-dependent maturation in ADA-deficient mouse spleens.<\/jats:p>","DOI":"10.4049\/jimmunol.171.10.5562","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T18:22:42Z","timestamp":1398018162000},"page":"5562-5570","source":"Crossref","is-referenced-by-count":38,"title":["Impaired Germinal Center Maturation in Adenosine Deaminase Deficiency"],"prefix":"10.1093","volume":"171","author":[{"given":"Melissa B","family":"Aldrich","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical School , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilma","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical School , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical School , Houston, TX 77030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector","family":"Martinez-Valdez","sequence":"additional","affiliation":[{"name":"Department of Immunology, M. 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