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While genetic causes such as\n                      <jats:italic>CD40L<\/jats:italic>\n                      and\n                      <jats:italic>AICDA<\/jats:italic>\n                      mutations are well established, a detailed comparison of B cell maturation dynamics across HIGM subtypes remains limited.\u00a0To comprehensively characterize B cell immunophenotypes and functional responses in patients with HIGM and to delineate mutation-specific differences in B cell maturation and proliferation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Four patients with genetically confirmed HIGM (one\n                      <jats:italic>CD40L<\/jats:italic>\n                      and three homozygous\n                      <jats:italic>AICDA<\/jats:italic>\n                      mutations, c.70C&gt;T; p.R24W) and age- and sex-matched healthy controls were studied. Peripheral blood mononuclear cells were analyzed by multiparameter flow cytometry to define B cell subsets based on CD19, CD20, CD24, CD27, CD38, IgD, and IgM expression. B cell proliferation was assessed following CpG stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients exhibited a marked reduction of class-switched memory B cells (CD27\u207aIgD\u207b) and accumulation of naive B cells (CD27\u207bIgD\u207a), consistent with defective CSR. The\n                      <jats:italic>CD40L<\/jats:italic>\n                      -deficient patient demonstrated profound depletion of plasmablasts and precursor skewing, reflecting failure of germinal center formation. In contrast,\n                      <jats:italic>AID<\/jats:italic>\n                      patients showed preserved CD27 expression with variable expansion of transitional and plasmablast populations, suggesting intact T cell\u2013dependent activation but intrinsic failure of CSR. Functional assays revealed heterogeneous proliferative responses in\n                      <jats:italic>CD40L<\/jats:italic>\n                      deficiency and\n                      <jats:italic>AICDA<\/jats:italic>\n                      -deficient patient, but impaired proliferation in another\n                      <jats:italic>AICDA<\/jats:italic>\n                      -deficient individual, highlighting inter-individual variability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Detailed immunophenotyping reveals distinct B cell maturation arrest points in\n                      <jats:italic>CD40L<\/jats:italic>\n                      - versus\n                      <jats:italic>AICDA<\/jats:italic>\n                      -associated HIGM. Flow cytometric analysis of B cell subsets provides valuable insights into disease mechanisms, supports differential diagnosis, and may inform clinical monitoring and therapeutic decision-making in HIGM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10875-026-02046-6","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:44:08Z","timestamp":1783572248000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering B cell Maturation Dynamics in Hyper-IgM Syndromes"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-1145","authenticated-orcid":false,"given":"Hande","family":"\u00dc\u00e7ler \u00c7\u0131nar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0187-3810","authenticated-orcid":false,"given":"Murat","family":"Cansever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-1685","authenticated-orcid":false,"given":"\u015eerife","family":"Erdem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-8658","authenticated-orcid":false,"given":"Abdullah","family":"Ar\u0131k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-0686","authenticated-orcid":false,"given":"Ahmet","family":"Eken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"issue":"2","key":"2046_CR1","first-page":"101","volume":"3","author":"LD Notarangelo","year":"1992","unstructured":"Notarangelo LD, Duse M, Ugazio AG. 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