European Journal of Immunology最新文献

Contrary to short-lived plasma cells, which survive only 3–5 days, long-lived plasma cells (LLPCs) contribute to the humoral memory of the body and thus also to many antibody-related diseases. The ability of plasma cells to persist over months, years, and even a lifetime has been demonstrated in vivo. Yet, the in vitro culture of human primary bone marrow-derived plasma cells has been limited to a few days. Here, we establish culture conditions for human primary bone marrow-derived plasma cells for 21 days. Plasma cells and stromal cells are isolated from human bone marrow and cultured in 2D or a 3D ceramic scaffold. The plasma cells’ survival and antibody secretion depend on direct contact with stromal cells. The culture promotes CD19-negative PCs. Inhibition of the PI3K or NF-kappaB pathways using chemical inhibitors reduced the survival of the plasma cells. These results underline the supportive role of the stromal cells for the survival of the LLPC and confirm mechanisms that were identified in mouse LLPCs also for human LLPCs. The culture described here will promote further studies to deepen our understanding of the human LLPC.

Our cover features images related to flow cytometry techniques widely used for analysis of function and phenotypes of major human and murine immune cell subsets, superimposed on a multidimensional immune cell population scatter plot. These images are taken from the third edition of EJI's Flow Cytometry Guidelines by Cossarizza et al., a comprehensive resource prepared by flow cytometry and immunology research experts from around the world.

Allergen-specific antibodies, particularly of the IgE class, are a hallmark of many allergic diseases. Yet paradoxically, (1) a proportion of healthy individuals possess allergen-specific IgE without clinical signs of allergy; (2) some, but not all, allergic individuals develop a more severe disease over time or fail to respond to allergen-specific immunotherapy; and (3) allergen-specific IgG antibodies can inhibit IgE-mediated responses but they can also induce allergic reactions. In this review, we discuss the occurrence of and transition between nonpathogenic and pathogenic allergen-specific antibody responses in the light of a two-stage model. We recapitulate different factors and scenarios that may induce different inflammatory conditions and qualitatively distinct allergen-specific T- and B-cell responses, influencing IgE origins and affinities, IgE/IgG(4) ratios, IgG effector functions, antibody glycosylation patterns, Fc and glycan-binding receptor expression and involvement, and ultimately their propensity to elicit allergic responses. Differences in these antibody characteristics may determine the onset of symptomatic allergy and the severity or remission of the disease.

B cells with low or absent expression of CD21 (CD21^lo B cells) gained attention due to their expansion in the peripheral blood of patients with immune-mediated, rheumatic diseases. This is not only observed in typical autoimmune diseases like systemic lupus erythematosus and Sjögren's disease (SjD) but also in radiographic axial spondyloarthritis (r-axSpA), which is considered an autoinflammatory disease. To gain more insight into the origins of the heterogeneous CD21^lo B-cell population, and its relation to the plasmablast (PB) compartment, we profiled the B-cell-receptor (BCR) repertoire in CD27⁻ and CD27⁺ fractions of CD21^lo B cells and early PBs using next-generation sequencing. Populations were sorted from peripheral blood of healthy individuals, SjD patients, and r-axSpA patients (n = 10 for each group). In healthy individuals and both patient groups, our findings indicate that CD27⁻CD21^lo B cells, which exhibit few mutations in their BCR, may develop into CD27⁺CD21^lo B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27⁻CD21^lo B cells in SjD and r-axSpA patients and clonal relationships with both CD27⁺CD21^lo B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics.

The CD8 co-receptor exists as both an αα homodimer, expressed on subsets of specialized lymphoid cells, and as an αβ heterodimer, which is the canonical co-receptor on cytotoxic T-cells, tuning TCR thymic selection and antigen-reactivity in the periphery. However, the biophysical parameters governing human CD8αβ interactions with classical MHC class I (MHCI) and unconventional MHC-like molecules have not been determined. Using hetero-dimerized Fc-fusions to generate soluble human CD8αβ, we demonstrate similar weak binding affinity to multiple different MHCI alleles compared with CD8αα. We observed that both forms of CD8 bound to certain alleles with stronger affinity than others and found that the affinity of thymically selected TCRs was inversely associated with the affinity of the CD8 co-receptor for the different alleles. We further demonstrated the binding of CD8αα and CD8αβ to the unconventional MHC-like molecule, MHCI-related protein 1, with a similar affinity as for classical MHCI, but no interaction was observed for the other unconventional MHC-like molecules, CD1a, b, c, or d. In summary, this is the first characterization of human CD8αβ binding to MHCI and MHC-like molecules that revealed an intriguing relationship between CD8 binding affinity for different MHCI alleles and the selection of TCRs in the thymus.