{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:15:06Z","timestamp":1787015706982,"version":"build-2736575974"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":1920,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D18CA-413"],"award-info":[{"award-number":["D18CA-413"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D18CA\u2010413"],"award-info":[{"award-number":["D18CA\u2010413"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>English bulldogs disproportionally develop an expansion of small B-cells, which has been interpreted as B-cell chronic lymphocytic leukemia (BCLL). However, clonality testing in these cases has often not been supportive of neoplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>English bulldogs have a syndrome of nonneoplastic B-cell expansion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>Eighty-four English bulldogs with small-sized CD21+ B-cell lymphocytosis in the blood as determined by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective study. We characterized this syndrome by assessing B-cell clonality, clinical presentation, flow cytometric features, and immunoglobulin gammopathy patterns. We identified 84 cases with CD21+ lymphocytosis among 195 English bulldogs with blood samples submitted to the Colorado State University-Clinical Immunology laboratory for immunophenotyping between 2010 and 2019. Flow cytometry features were compared to normal B-cells and BCLL cases. PCR for antigen receptor rearrangements (PARR) by multiple immunoglobulin primers was performed to assess B-cell clonality. A subset of cases with gammopathy were examined by protein electrophoresis, immunofixation, and immunoglobulin subclass ELISA quantification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy percent (58\/83) of cases had polyclonal or restricted polyclonal immunoglobulin gene rearrangements, suggesting nonmalignant B-cell expansion. The median age of all dogs in the study was 6.8\u2009years and 74% were male. The median (range) lymphocyte count was 22\u2009400\/\u03bcL (2000-384\u2009400\/\u03bcL) and B-cells had low expression of class II MHC and CD25. Splenomegaly or splenic masses were detected in 57% (26\/46) of cases and lymphadenopathy in 11% (7\/61). Seventy-one percent (52\/73) of cases had hyperglobulinemia and 77% (23\/30) with globulin characterization had IgA\u2009\u00b1\u2009IgM polyclonal or restricted polyclonal gammopathy patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Polyclonal B-cell lymphocytosis in English bulldogs is characterized by low B-cell class II MHC and CD25 expression, splenomegaly and hyperglobulinemia consisting of increased IgA\u2009\u00b1\u2009IgM. We hypothesize that this syndrome has a genetic basis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.15913","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T09:23:14Z","timestamp":1602753794000},"page":"2622-2635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Polyclonal B-cell lymphocytosis in English bulldogs"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1435-8532","authenticated-orcid":false,"given":"Emily D.","family":"Rout","sequence":"first","affiliation":[{"name":"Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Microbiology, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-8788","authenticated-orcid":false,"given":"A Russell","family":"Moore","sequence":"additional","affiliation":[{"name":"Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Microbiology, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Burnett","sequence":"additional","affiliation":[{"name":"Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Department of Microbiology, , Fort Collins, Colorado,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia D.","family":"Labadie","sequence":"additional","affiliation":[{"name":"Public Health Sciences Division, Fred Hutchinson Cancer Research Center , Seattle, Washington,","place":["USA"]},{"name":"University of Washington Department of Epidemiology, , Seattle, Washington,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly 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