Work

Transcriptomic Consequences of CD74 Knockout in Raji and Meljuso Tumor Cells

Year: 2026

Type: preprint

Abstract: The invariant chain (CD74) plays a crucial role in MHC-II antigen presentation and intracellular trafficking, as well as immunological signaling and cell survival. Although its canonical function is well established, the global transcriptional consequences of CD74 loss remain unclear. Here, we used RNA sequencing to characterize the impact of CD74 knockout in Raji and Meljuso cells and compared with their respective wild-type counterparts. CD74 depletion induced extensive transcriptional reprogramming in both models, as revealed by principal component and differential expression analyses. Functional enrichment and gene set enrichment analyses showed that loss of CD74 affects antigen processing and presentation pathways. In parallel, immune signaling and intracellular trafficking networks were significantly altered. Notably, the transcriptional response was highly context dependent. In Raji cells, CD74 knockout led to suppression of antigen presentation pathways and activation of stress-response and protein-folding programs. In contrast, Meljuso cells exhibited robust induction of interferon signaling and antiviral response pathways. Comparative analysis identified both shared and divergent gene expression programs, including genes displaying inverse expression patterns between the two cell lines. Pathway enrichment analysis further revealed remodeling of key signaling networks, including B cell receptor signaling and immune regulatory pathways. Together, these results indicates that CD74 works as a context-dependent regulator of transcriptional and signaling networks. Its loss triggers distinct compensatory responses depending on cellular background, with potential implications for immune regulation and tumor biology. This study expands the understanding of CD74 beyond its original role in antigen presentation and highlights its broader impact on cellular homeostasis.

Source: Research Square

DOI: 10.21203/rs.3.rs-10325671/v1

Authors: Shivani Tyagi, Manoj Kumar B S, Oddmund Bakke, Swarupa Panda, Niladri Bhusan Pati

Institutions: Kasturba Medical College, Manipal, Manipal Academy of Higher Education, University of Oslo

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Indian Council of Medical Research, Universitetet i Oslo, Norges Forskningsråd