{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:40:40Z","timestamp":1788576040488,"version":"build-2803163510"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    B-1 cells are a subset of B cells with innate-like properties discovered in the early 1980s in mice. They are important contributors to homeostasis, partly because they secrete natural antibodies with regulatory and scavenging functions. They mainly reside in the pleural and peritoneal cavities, as well as in the spleen and lamina propria of the intestinal mucosa. They differ from conventional (B-2) cells in their ontogeny, phenotype, and functions. In humans, the search for a B-1 cell counterpart began shortly after their discovery in mice, but several difficulties hindered their identification, due to inaccurate phenotypic markers and limited accessibility to the sites where they reside. In this review, we discuss the findings regarding B-1 cells in humans and compare them with murine B-1 cells. In 2011, human B-1\u2013like cells were identified based on functional features and were found to have a CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD20\n                    <jats:sup>+<\/jats:sup>\n                    (or IgM\n                    <jats:sup>+<\/jats:sup>\n                    ) CD27\n                    <jats:sup>+<\/jats:sup>\n                    CD38\n                    <jats:sup>low\/int<\/jats:sup>\n                    CD43\n                    <jats:sup>+<\/jats:sup>\n                    phenotype. This discovery was vigorously debated, but their existence and equivalence to murine B-1 cells has gained acceptance in recent years. These human B-1 cells are present in blood, skin, pleural and peritoneal cavities, the spleen, and several fetal tissues. They exhibit tonic intracellular signaling and spontaneously secrete antibodies that share certain specificities with classical natural antibodies (e.g., against phosphorylcholine or bacterial polysaccharides). However, they also differ from murine B-1 cells in several aspects, including somatic hypermutation and spontaneous secretion of IgG. Several questions remain unresolved regarding their tissue residency, developmental origin during fetal life, and contribution to immune homeostasis. Moreover, evidence addressing their involvement in infectious, inflammatory, and immune-mediated diseases, remains limited and sometimes controversial, although most studies suggest a protective role. In this review, we critically examine these open questions, highlight areas of consensus and debate, and outline future directions necessary to better define the biology and clinical relevance of human B-1 cells.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1810144","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:47:08Z","timestamp":1776055628000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Do human B-1 lymphocytes truly exist?"],"prefix":"10.3389","volume":"17","author":[{"given":"M\u00f3nica Itzel","family":"Mart\u00ednez-Guti\u00e9rrez","sequence":"first","affiliation":[{"name":"Plan de Estudios Combinados en Medicina, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irma","family":"Ca\u00f1edo-Solares","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Experimental, Subdirecci\u00f3n de Medicina Experimental Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"G\u00f3mez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Enfermedades Osteoarticulares e Inmunol\u00f3gicas, Escuela Nacional de Medicina y Homeopat\u00eda, Instituto Polit\u00e9cnico Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana Monserrat","family":"Molina-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad An\u00e1huac M\u00e9xico, Huixquilucan","place":["Estado de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Flores-Rabasa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad An\u00e1huac M\u00e9xico, Huixquilucan","place":["Estado de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Alejandro","family":"Magdaleno-Villanueva","sequence":"additional","affiliation":[{"name":"Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Israel","family":"Le\u00f3n-Pedroza","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad An\u00e1huac M\u00e9xico, Huixquilucan","place":["Estado de M\u00e9xico, Mexico"]},{"name":"Hospital General de M\u00e9xico \u201cDr. Eduardo Liceaga\u201d, Secretar\u00eda de Salud","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores","family":"Correa","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencias de la Salud, Facultad de Ciencias de la Salud, Universidad An\u00e1huac M\u00e9xico, Huixquilucan","place":["Estado de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","unstructured":"Cellular and molecular immunology\n          \n          \n            \n              Abbas\n              AK\n            \n            \n              Lichtman\n              AH\n            \n            \n              Shiv\n              P\n            \n          \n          \n          2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700943","article-title":"A hard(y) look at B-1 cell development and function","volume":"199","author":"Baumgarth","year":"2017","journal-title":"J Immunol Baltim Md 1950"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200944","article-title":"Non-canonical B cells: characteristics of uncharacteristic B cells","volume":"211","author":"Haas","year":"2023","journal-title":"J Immunol Baltim Md 1950"},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1034\/j.1600-065x.2000.017520.x","article-title":"B-1 cells: the lineage question revisited","volume":"175","author":"Herzenberg","year":"2000","journal-title":"Immunol Rev"},{"key":"B5","volume-title":"B-Cell Immunophenotyping. 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