@article{ZipfelEyrichSchlegeletal.2016,
  author    = {Zipfel, Julian and Eyrich, Matthias and Schlegel, Paul-Gerhardt and Wiegering, Verena},
  title     = {Disturbed B cell and DC-Homeostasis in Pediatric cGVHD Patients-Cocultivation Experiments and Review of the Literature},
  series = {Clinics in Oncology},
  volume    = {1},
  journal   = {Clinics in Oncology},
  number    = {1097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147914},
  year      = {2016},
  abstract  = {B cells and DCs are suspected to play an important role in the pathogenesis of cGvHD, which is a serious complication of HSCT with high morbidity. It is characterized by immune responses of donor immune cells against recipient-derived antigens. athogenesis is not yet fully understood, however reconstitution of B cells after HSCT has similarities to physiologic ontogeny. Immunophenotyping and co-cultivation-experiments of B cells and DCs from pediatric patients with cGvHD as well as healthy donors were conducted. Significant differences between patients and healthy donors were observed with increased memory, transitional, CD69+ and CD86+ phenotype and lower levels of na{\"i}ve B cells due to apoptosis. Co-cultivation revealed this to be primarily B cell-dependent without major effects of and with DCs. There was a decreased CD11c- phenotype in patients and less apoptosis of DCs. Our data suggest a disturbed homeostasis in B cells with increased memory phenotype in patients, whereas DCs could not influence these differences, therefore DCs are not imposing as promising targets. B cell-dependent approaches should be further investigated.},
  language  = {en}
}
@article{DirksAndresPauletal.2023,
  author    = {Dirks, Johannes and Andres, Oliver and Paul, Luisa and Manukjan, Georgi and Schulze, Harald and Morbach, Henner},
  title     = {IgD shapes the pre-immune na{\"i}ve B cell compartment in humans},
  series = {Frontiers in Immunology},
  volume    = {14},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2023.1096019},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304758},
  year      = {2023},
  abstract  = {B cell maturation and immunoglobulin (Ig) repertoire selection are governed by expression of a functional B cell receptor (BCR). Na{\"i}ve B cells co-express their BCR as IgM and IgD isotype. However, the role of the additionally expressed IgD on na{\"i}ve B cells is not known. Here we assessed the impact of IgD on na{\"i}ve B cell maturation and Ig repertoire selection in 8 individuals from 3 different families with heterozygous loss-of-function or loss-of expression mutations in IGHD. Although na{\"i}ve B cells from these individuals expressed IgM on their surface, the IGHD variant in heterozygous state entailed a chimeric situation by allelic exclusion with almost half of the na{\"i}ve B cell population lacking surface IgD expression. Flow cytometric analyses revealed a distinct phenotype of IgD-negative na{\"i}ve B cells with decreased expression of CD19, CD20 and CD21 as well as lower BAFF-R and integrin-β7 expression. IgD-negative B cells were less responsive in vitro after engaging the IgM-BCR, TLR7/9 or CD40 pathway. Additionally, a selective disadvantage of IgD-negative B cells within the T2 transitional and mature na{\"i}ve B cell compartment as well as reduced frequencies of IgMlo/- B cells within the mature na{\"i}ve B cell compartment lacking IgD were evident. RNA-Ig-seq of bulk sorted B cell populations showed an altered selection of distinct VH segments in the IgD-negative mature na{\"i}ve B cell population. We conclude that IgD expression on human na{\"i}ve B cells is redundant for generation of na{\"i}ve B cells in general, but further shapes the naive B cell compartment starting from T2 transitional B cells. Our observations suggest an unexpected role of IgD expression to be critical for selection of distinct Ig VH segments into the pre-immune Ig repertoire and for the survival of IgMlo/- na{\"i}ve B cells known to be enriched in poly-/autoreactive B cell clones.},
  language  = {en}
}