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• Guslund, Naomi Croft; Jonsson, Alexandra; Krabberød, Anders Kristian; Porras, Adrian Lopez; Nørstebø, Simen Foyn & Sørum, Henning [Show all 9 contributors for this article] (2026). IgM-mediated protection drives early B-cell activation and mucosal containment of Vibrio anguillarum in Atlantic cod (Gadus morhua). Frontiers in Immunology. 17. doi: 10.3389/fimmu.2026.1771403. Full text in Research Archive Show summary

  Background: Atlantic cod lack functional MHC class II and CD4, raising fundamental questions about how vaccination generates protection in this species. Methods: We combined single-cell transcriptomic profiling of splenic cells with qRT-PCR across complementary active vaccination and passive serum-transfer experiments to define cellular and transcriptional correlates of immunity to Vibrio anguillarum. Results: Bath-vaccinated fish and recipients of immune serum showed effective containment of infection, with bacterial signals largely restricted to gills and minimal detection in spleen or head kidney, whereas naïve fish frequently developed high systemic bacterial loads by day 3 post-infection. All groups exhibited increased splenic macrophage abundance following challenge, but only naïve fish showed strong and sustained inflammatory activation, consistent with their higher pathogen burden. Vaccinated fish and immune-serum recipients displayed only transient or weak myeloid responses despite similar early neutrophil activation. Across both experimental models, a transcriptionally distinct B-cell subset expanded at the peak of infection. This population showed increased immunoglobulin and MHC class I expression together with innate sensing features, consistent with an activated B-cell state. Although this B-cell subset increased in all groups, the largest expansions were observed in vaccinated fish and immune-serum recipients. Overall, these findings are consistent with antigen-specific IgM enhancing early B-cell activation and contributing to protection against V. anguillarum through coordinated humoral and innate-like B-cell responses. Discussion: These findings identify an antibody-driven mode of immune coordination that operates independently of classical CD4+ T-cell help and provide insight into how effective vaccination can be achieved in vertebrates with divergent adaptive immune architectures.

• Jonsson, Alexandra; Porras, Adrian Lopez; Nørstebø, Simen Foyn; Guslund, Naomi Croft; Sørum, Henning & Qiao, Shuo-Wang [Show all 7 contributors for this article] (2025). Protective IgM-mediated immunity against Vibrio anguillarum in Atlantic cod with evolutionary losses of mhc class II and cd4. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1579541. Full text in Research Archive Show summary

  The unique adaptive immune system of the Atlantic cod ( Gadus morhua ), with genetic loss of the mhc class II and cd4 , poses questions about the protective role of specific antibodies in this species. We investigate the IgM response against Vibrio anguillarum , a common pathogen in aquaculture. Juvenile Atlantic cod were bath-immunized with formalin-fixed V. anguillarum serotype O2a. Vaccinated cod were fully protected against lethal vibriosis when challenged by immersion with serotype O2a and partially protected against challenge with serotype O2b. Serum IgM from immunized cod reacted specifically with V. anguillarum O2a in ELISA, with some crossreactivity towards the O2b serotype. Bath-immunized cod were also protected against intracelomic challenge with V. anguillarum O2a, supporting the induction of systemic immunity by bath vaccination. Passive transfer experiments were conducted to evaluate the protective efficacy of IgM. Naive cod that received total serum or purified IgM from immunized donors were protected against lethal vibriosis; whereas, naive cod that received naive serum were not protected. Western blotting revealed that these protective antibodies recognized a proteinase K-sensitive antigen rather than lipopolysaccharides. These insights enhance our understanding of cod immunity and provide guidance for developing future vaccination strategies in aquaculture.

• Porras, Adrian Lopez; Jonsson, Alexandra; Qiao, Shuo-Wang & Johansen, Finn-Eirik (2025). Sustained T cell-independent type 2 antibody response in a naturally MHC II-deficient teleost fish. Developmental and Comparative Immunology. ISSN 0145-305X. 164. doi: 10.1016/j.dci.2025.105330. Full text in Research Archive Show summary

  Atlantic cod (Gadus morhua) is well-known to show poor specific antibody responses after immunization, despite having high natural IgM levels. Unlike mammals and nearly all examined other vertebrates, cod lack the MHC II-CD4 axis required for T cell-dependent (TD) antibody responses. We evaluated the cod's antibody response to hapten carriers inducing T cell-independent (TI) and TD responses in mammals. Remarkably, cod generated strong hapten-specific IgM levels against hapten linked to the TI-2 antigens ficoll or dextran. Specific IgM levels plateaued 6–9 weeks after a single immunization and remained stable for six months. The serum half-life of IgM was 4 days, indicating continuous IgM production during this period. These findings reveal unique immune mechanisms in Atlantic cod, enhancing our understanding of vertebrate immunology and aiding the development of novel vaccination strategies in aquaculture.

• Foss, Stian; Jonsson, Alexandra; Bottermann, Maria; Watkinson, Ruth; Lode, Heidrun Elisabeth & McAdam, Martin Berner [Show all 10 contributors for this article] (2022). Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge. Science immunology. 7(70). doi: 10.1126/sciimmunol.abj1640. Full text in Research Archive
• Foss, Stian; Bottermann, Maria; Jonsson, Alexandra; Sandlie, Inger; James, Leo C. & Andersen, Jan Terje (2019). TRIM21-From intracellular immunity to therapy. Frontiers in Immunology. 10:2049, p. 1–14. doi: 10.3389/fimmu.2019.02049. Full text in Research Archive Show summary

  Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.

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• Jonsson, Alexandra; Johansen, Finn-Eirik; Qiao, Shuo-Wang & Baalsrud, Helle Tessand (2025). Humoral immunity in Atlantic cod: a tale of antibodies in a fish missing the MHC II-CD4 pathway. Universitetet i Oslo. Full text in Research Archive Show summary

  Vaccines are designed to stimulate immune memory and protection, and antibody titers remain key indicators of vaccine efficacy. The production of high-affinity, long-lived antibodies relies on T cell-dependent mechanisms, where B cells interact with CD4+ T helper cells via peptide-MHC II presentation. This interaction drives germinal center formation, class switching, and memory development. However, Atlantic cod (Gadus morhua) present an immunological paradox. Despite their capacity to thrive in pathogen-rich environments and receive functional protection from certain vaccines, cod mount weak antibody responses and lack both the mhc class II locus and a functional cd4 gene. Long before this was confirmed by whole-genome sequencing by Star et al. in 2011, Pilström posed a prescient question: “If we pose the hypothetical question: ‘What would an antibody response look like in the absence of MHC class II molecules?’ an acceptable answer would be: ‘Very much like the antibody response of the cod.’” — Pilström, 2005 This thesis explores how cod generate specific and protective antibodies in the absence of canonical T cell-dependent pathways. We first developed monoclonal and polyclonal antibodies against cod IgM, enabling sensitive detection across multiple immunological methods. Using these tools, we showed that cod produced strong and sustained IgM responses to T cell-independent type 2 antigens, while T cell-dependent and T cell-independent type 1 responses were minimal. We then vaccinated cod with Vibrio anguillarum O2a and challenged them with both O2a and O2b strains, observing full and partial protection, respectively. This immunization induced specific IgM antibodies against O2a that cross-reacted with O2b. These antibodies recognized proteinaceous rather than lipopolysaccharide antigens and conferred protection when transferred to naive recipients. Yet, our efforts to define antibody effector functions was challenging. We found that the V. anguillarum O2a strain was resistant to complement-mediated killing, and that there was no measured differences in phagocytic activity in presence of either naive or immune sera. Altogether, this work shows that cod possess a functional but unconventional humoral immune system. It challenges assumptions about the universality of the MHC II–CD4 axis and highlights the evolutionary plasticity of adaptive immunity.

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