{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T06:21:42Z","timestamp":1773642102324,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["NIH AI134027 (HWS), , AI163555 (HWS), AI175868 (HWS), R56AG076730 (MK)"],"award-info":[{"award-number":["NIH AI134027 (HWS), , AI163555 (HWS), AI175868 (HWS), R56AG076730 (MK)"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Peritoneal cavity (PerC) B cells arise via a specific set of ontogenetic and antigen-driven selection pressures. A large portion of the PerC B-1 population, including B-1a and B-1b cells, is fetal-derived and thus, due to a lack of N nucleotide addition, produces an immunoglobulin repertoire that is characteristically germline-encoded. While conventional B-2 cells depend on efficient pairing of surrogate light chain (SLC) and \u03bc Heavy Chain (HC) to pass through the preBCR checkpoint, the extent to which the passage of the B-1 population through the preBCR checkpoint affects the composition of its repertoire has remained an open question. In this work, we used mice deficient in \u03bb5, a key component of the SLC, to test whether the absence of preBCR selection would yield natural, germline encoded, PerC B-1 CDR-H3 repertoires similar to WT. And, if not, whether a more WT-like repertoire at the protein level would be recreated by convergent cellular evolution. We found that the absence of preBCR selection led to categorical differences in DH-specific gene segment usage, RF preference, and N addition in PerC B-1a, B-1b, and B-2 CDR-H3s when compared to WT. Despite this marked divergence in nucleotide sequence, at the translated amino acid level, the B-1a CDR-H3 repertoire generated in the absence of preBCR selection exhibited partial convergence to the WT sequence, most notably with selection for tyrosine; this phenomenon was less apparent in B-1b and B-2 cells. This convergence was not evident at the nucleotide level and did not restore the underlying VDJ architecture. These results suggest that while the initial CDR-H3 repertoire is altered genetically in the absence of preBCR selection, natural self-antigen selection and self-renewal in the B-1a compartment promote the creation of a CDR-H3 repertoire that has considerable overlap in amino acid sequence with its wild-type counterpart.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1733041","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:23:35Z","timestamp":1773638615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Absent the pre-B cell receptor checkpoint, the B-1a immunoglobulin CDR-H3 repertoire normalizes by convergent selection"],"prefix":"10.3389","volume":"17","author":[{"given":"Lucas Tostes Costa","family":"Vaz","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]},{"name":"Program in 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