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B cell development is tightly regulated, ensuring the generation of distinctive B cell clones, each carrying a fixed B cell receptor and therefore antigen specificity. Defects in B cell development can underlie a variety of clinical phenotypes, including immunodeficiency, autoimmunity, and B cell leukemia. The study of human genetic variation has enabled the discovery of critical pathways for immune cell development, differentiation, and generation of immune repertoire diversity. Here, we focus on the complete allelic spectrum impacting central B cell development, including rare and common genetic variation, to shed light on unique and shared mechanisms underlying predisposition to B cell lymphopenia, autoimmunity, and leukemia.<\/jats:p>","DOI":"10.70962\/jhi.20250042","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T02:21:24Z","timestamp":1749608484000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Human genetic influences on early B cell development"],"prefix":"10.70962","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8573-6820","authenticated-orcid":true,"given":"Anna-Lena","family":"Neehus","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dvg7y05","id-type":"ROR","asserted-by":"publisher"}],"name":"Boston Children\u2019s Hospital, Harvard Medical School 1 Division of Hematology\/Oncology, , Boston, MA,","place":["USA"]},{"name":"Dana-Farber Cancer Institute, Harvard Medical School 2 Department of Pediatric Oncology, , Boston, MA,","place":["USA"]},{"name":"Howard Hughes Medical Institute 3 , Boston, MA,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard 4 , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-5318","authenticated-orcid":true,"given":"Neil","family":"Romberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"publisher"}],"name":"Children\u2019s Hospital of Philadelphia 5 Division of Immunology and Allergy, , Philadelphia, PA,","place":["USA"]},{"name":"Perelman School of Medicine 6 Department of Pediatrics, , Philadelphia, PA,","place":["USA"]},{"name":"Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania 7 , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-443X","authenticated-orcid":true,"given":"Vijay G.","family":"Sankaran","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dvg7y05","id-type":"ROR","asserted-by":"publisher"}],"name":"Boston Children\u2019s Hospital, Harvard Medical School 1 Division of Hematology\/Oncology, , Boston, MA,","place":["USA"]},{"name":"Dana-Farber Cancer Institute, Harvard Medical School 2 Department of Pediatric Oncology, , Boston, MA,","place":["USA"]},{"name":"Howard Hughes Medical Institute 3 , Boston, MA,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard 4 , Cambridge, MA,","place":["USA"]},{"name":"Harvard Stem Cell Institute 8 , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"2025062509452464700_bib1","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1126\/science.1086907","article-title":"Predominant autoantibody production by early human B cell precursors","volume":"301","author":"Wardemann","year":"2003","journal-title":"Science"},{"key":"2025062509452464700_bib2","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1172\/JCI73441","article-title":"An autoreactive antibody from an SLE\/HIV-1 individual broadly neutralizes HIV-1","volume":"124","author":"Bonsignori","year":"2014","journal-title":"J. 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