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MBCs arise via both T cell\u2013dependent and \u2013independent routes and while CD4+ T cells are not required for their formation, it is still not clear if or how initial T:B-cell interactions influence the molecular programming and diversity of T cell\u2013independent MBCs. To address this, we characterized MBCs that form in response to influenza infection in major histocompatibility complex class II knockout (MHCII-KO) mice, which lack CD4+ T cells. Consistent with T cell\u2013independent responses, the MBCs that formed in MHCII-KO mice were reduced in number and did not acquire surface expression of CCR6 and class-switched BCR. Transcriptional profiling identified cytokine- and activation-induced genes that were reduced in expression in MHCII-KO MBCs compared to wild type (WT). Adoptive transfer of MHCII-KO B cells into WT hosts, which cannot receive peptide\/MHCII\u2013TCR cognate interactions, revealed an ability of MHCII-KO cells to form MBCs and ASCs. Single-cell RNA sequencing revealed minimal transcriptional differences between MHCII-KO and WT MBCs, indicating that cognate CD4+ T-cell interactions provide limited early programming instruction to MBCs. MHCII-KO MBCs were able to clonally expand, class-switch, and form the same diverse transcriptional clusters as WT. These data indicate that early differentiating MBCs can seed a diverse pool of MBC populations in response to influenza infection independent of cognate T-cell help.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag054","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:04:09Z","timestamp":1776625449000},"source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional programming of early-forming memory B cells arises independently of cognate CD4+ T-cell interactions"],"prefix":"10.1093","volume":"215","author":[{"given":"Keenan J","family":"Wiggins","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Elliott","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakeenah L","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbey O","family":"Padilla-Quirarte","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly J","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-3663","authenticated-orcid":false,"given":"Jobaida","family":"Akther","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham , Birmingham, AL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy D","family":"Randall","sequence":"additional","affiliation":[{"name":"Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham , Birmingham, AL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M","family":"Boss","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-8504","authenticated-orcid":false,"given":"Christopher D","family":"Scharer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"2026041915040470400_vkag054-B1","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1084\/jem.20110740","article-title":"Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants","volume":"208","author":"Purtha","year":"2011","journal-title":"J Exp Med"},{"key":"2026041915040470400_vkag054-B2","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/ni.1814","article-title":"Multiple layers of B cell memory with different effector 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