Jchain, also known as the immunoglobulin joining chain, is essential for the assembly and transport of Immunoglobulin M (IgM) and Immunoglobulin A (IgA), playing a pivotal role in both humoral and mucosal immunity [1]. It is involved in the formation of polymeric immunoglobulins, and its associated pathways are crucial for the normal functioning of the immune system. Genetic models, such as mouse models, are valuable tools for studying Jchain's functions.

In a Jchain-DTR mouse model, antibody-secreting cells (ASCs) expressing high levels of cell surface diphtheria toxin receptor (DTR) under the control of the endogenous Jchain locus were acutely depleted following diphtheria toxin treatment. This model was used to track ASC reconstitution in three distinct organs, providing insights into ASC differentiation kinetics [3]. In multiple myeloma (MM), the high expression of Jchain makes Jchain-derived peptides presented in HLA molecules suitable antigens for T-cell therapy. T-cell clones specific for Jchain peptides were isolated, and their TCRs transferred to CD8 T cells. These Jchain TCR T cells could recognize and lyse JCHAIN-positive MM cells, both in vitro and in a pre-clinical in vivo model, reducing the tumor burden [2]. In IgA nephropathy, the up-regulation of JCHAIN in mesangial cells provides insights into the trigger mechanism for the dimerization and deposition of IgA1 in situ [4].

In conclusion, Jchain is vital for the proper functioning of the immune system, especially in the context of IgM and IgA-related immune responses. Mouse models like Jchain-DTR mice have been instrumental in understanding ASC biology, and the role of Jchain in diseases such as multiple myeloma and IgA nephropathy. These findings contribute to a better understanding of immune-related diseases and may lead to the development of novel therapeutic strategies.