Fig 2: Proportion of Tfh and Breg cells in gastric cancer patients. Blood samples were collected from 36 cases of gastric cancer patients and 18 cases of healthy people. Representative flow cytometric results were shown. Tfh cells were classified as CXCR5+CD4+ T cells (a), while Breg cells were classified as CD19+CD24hiCD38hi cells (c). Compared to control individuals, significantly increased percentage of Tfh cells (b) and Breg cells (d) was found in gastric cancer patients (P < 0.05). A positive association between Tfh% and Breg% was found in gastric cancer patients (e, P < 0.05), rather than in the healthy group (f, P > 0.05). Higher CXCL13 level was in the gastric cancer group than in the healthy group (g, P < 0.05). IL-21 and IL-10 levels have no significant difference (h and i, P > 0.05). Tfh: follicular help T cells; Breg: regulatory B cells; CXCL13: C-X-C motif chemokine ligand 13; IL-21: interleukin-21; IL-10: interleukin-10; ∗: <0.05; ∗∗: <0.01; ns: no significance.

Fig 3: The expansion of hCD4+hPD-1highhCXCR5-hCCR2+ Tph cells was specifically observed in iMCD-NOS NSG mice.a A representative FACS plot of hCD45+ cells in the spleen of iMCD-NOS NSG3 mice. Human CD3+ CD4+ cells were analyzed for PD-1 and CXCR5 expression levels. b The frequencies of hPD-1highhCXCR5− cells among CD3+CD4+ human T cells in NSG mice reconstituted with normal human hematopoiesis via xenotransplantation of CB-derived CD34+ HSPCs (left, black, n = 3) and four independent iMCD-NOS NSG mice (right, red, NSG1: n = 4, NSG2: n = 6, NSG3: n = 6 and NSG5: n = 4). Two-group comparison between the iMCD group and the control group was performed using unpaired two-sided t test (P = 7.99 × 10−9). Error bar represented as mean ± SD. c Representative FACS plot of hCCR2 expression in hPD-1highhCXCR5- Tph cells in the spleen of iMCD-NOS NSG2 mice (P2). d Comparison of the frequencies of CD3+CD4+PD-1highCXCR5− Tph cells and CD3+CD4+PD-1highCXCR5+ Tfh cells in the reactive LN (C1, C6, C7, C8, and C9: black, n = 5) and iMCD-NOS LN samples (P4, P7, P8, P9, P10, and P11: red, n = 6). Comparison between the two groups was analyzed with two-tailed unpaired t test. (Tph: P = 0.01358 and Tfh: P = 0.6635) Error bar represented as mean ± SE. e Heatmap analysis of human (left) and mouse (right) cytokines and chemokines in the sera of NSG mice reconstituted with normal human hematopoiesis by xenotransplantation of CB-derived CD34+ HSPCs (n = 3) (left) and LN cells from Patient 2 (n = 5). f Comparison of the levels of human cytokines and chemokines in the serum of the original patient (P2) and sera of iMCD-NOS NSG2 mice transplanted with LN cells from the same patient. g Representative intracellular staining of CXCL13 expression in CD4+PD-1highCXCR5− Tph cells from the LN of the patient with iMCD-NOS(P1) and PB of patient with iMCD-NOS (P6). **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are provided as a Source Data.

Fig 4: A schematic summary of the proposed pathogenesis of iMCD-NOS in our PDX model.Our xenotransplantation experiments revealed that the T-B interaction is required for the development of iMCD-like systemic inflammation in vivo with the elevation of human gamma-globulin. Aberrantly expanded CD4+PD-1highCXCR5-CCR2+ Tph cells actively secrete CXCL13 and promote the migration of B cells toward inflamed sites. Through interaction with Tph cells, migrated B cells differentiate into plasmablasts and initiate the secretion of human gamma-globulin, cytokines, and chemokines, leading to systemic inflammation. Thus, iMCD-NOS represents an abnormal immunoregulatory disorder in which the aberrant immunological synapse consisting of T-B interactions plays a critical role in disease initiation and exacerbation.

Fig 5: IgE and inflammatory cytokine levels between HRV-positive and HRV-negative groups in non-AIT AR subjects. (A) Total serum IgE levels in HRV-positive group (n = 54) vs HRV-negative group (n = 49). (B) Total nasal lavage IgE levels in HRV-positive group (n = 54) vs HRV-negative group (n = 49). (C–F) Nasal lavage levels of CXCL13, IL-25, IL-4, and IL-5 cytokines in HRV-positive group (n = 54) vs HRV-negative group (n = 49). Data are presented as the mean ± SD. *P < 0.05 based on two-tailed Mann–Whitney U-tests (A and B) and two-tailed t-test (C–F).