Do human B-1 lymphocytes truly exist?
Open accessAbstract
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–like cells were identified based on functional features and were found to have a CD19 + CD20 + (or IgM + ) CD27 + CD38 low/int CD43 + 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.
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Subsequent studies challenged both the phenotypic definition and quantification of human B1 cells, arguing CD27+CD43+ B cells represent a heterogeneous population overlapping with transitional, memory, and innate-like B cell subsets rather than a bona fide B1 equivalent.
“However, subsequent studies chal lenged both the phenotypic definition and the quantification of this population, with several groups arguing that CD27 + CD43 + B cells represent a heterogeneous population overlapping with transitional, memory, and innate-like B cell subsets rather than a bona fide B1 B cell equivalent [50].”
From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [50]
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Flagged first, then by citations
Research works printed but not linked: 2
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Cited by
Sorted by citations
Is there a role for B cells in Alzheimer's disease?
Charavner, E.-L., Fillatreau, S., & El Behi, M. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105154
Nair, M. A., Chandel, K., Shreevarsha, S., Premraj, S., Nithya, U., & Gayathri, M. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1906541
- Authors
- Martínez-Gutiérrez, M. I., Cañedo-Solares, I., Gómez-Chávez, F., Molina-López, L. M., Flores-Rabasa, R., Magdaleno-Villanueva, J. A., León-Pedroza, J. I., & Correa, D.
- Affiliations
- Universidad Nacional Autónoma de México (MX)
- Secretaria de Salud (MX)
- Laboratorio de Enfermedades Osteoarticulares e Inmunológicas, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional
- Universidad Anáhuac (MX)
- Instituto Politécnico Nacional (MX)
- Hospital General de México (MX)
- Corresponding author
- Correa, Dolores
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2026-04-13
- Volume
- 17
- Pages
- 1810144-1810144
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC13111098
- OpenAlex
- W7153997479
- Cited by
- 2
- References
- 129
- Citations by year
- 2026: 2
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- B-1 cells, natural antibodies, innate-like B cells, B2 cells, somatic hypermutation, IgG secretion, fetal development, tissue residency, immune homeostasis
- MeSH terms
- Animals, Homeostasis, Humans, B-Lymphocyte Subsets, Mice
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