Plasma Cell Alloantigen 1 and IL-10 Secretion Define Two Distinct Peritoneal B1a B Cell Subsets With Opposite Functions, PC1(high) Cells Being Protective and PC1(low) Cells Harmful for the Growing Fetus
FRONTIERS IN IMMUNOLOGY
Authors: Schumacher, Anne; Ehrentraut, Stefanie; Scharm, Markus; Wang, Hongsheng; Hartig, Roland; Morse, Herbert C., III; Zenclussen, Ana Claudia
Abstract
B cells possess various immuno regulatory functions. However, research about their participation in tolerance induction toward the fetus is just emerging. Accumulating evidence supports the idea that B cells can play seemingly conflicting roles during pregnancy, either protecting or harming the fetus. Previous findings indicated the presence of two different peritoneal B cell subsets, defined by the expression of the plasma cell alloantigen 1 (PC1) and with distinct immune modulatory functions. Here, we aimed to study the participation of these two B cell subsets, on pregnancy outcome in a murine model of disturbed fetal tolerance. The frequencies and cell numbers of peritoneal and splenic CD19(+) IL-10(+) and CD19(+) CD5(+) IL-10(+) PC1(+) cells were assessed in virgin as well as normal pregnant (NP) and abortion-prone (AP) females during the course of gestation. Peritoneal PC1(low) or PC1(high) B1a B cells were sorted, analyzed for their ability to secrete IL-10 and adoptively transferred into NP or AP females. On gestation day (gd) 12, the abortion rate as well as the frequencies and cell numbers of regulatory T cells, TH1 and TH17 cells were determined in spleens and decidua. In addition, mRNA expression of IL-10, TGF-beta, IFN-gamma, and TNF-alpha was analyzed in decidual tissue. Peritoneal CD19(+)IL-10(+) and CD19(+) CD5(+) IL-10(+) PC1(+) frequencies fluctuated during the progression of normal pregnancies while no significant changes were observed in spleen. AP females showed significantly reduced frequencies of both B cell populations and exhibited an altered peritoneal PC1(high)/PC1(low) ratio at gd10. Adoptive transfers of PC1(low) B1a B cells into NP females increased the abortion rate in association with a reduced splenic regulatory T/TH17 ratio. By contrast, the transfer of PC1high B1a B cells into AP females significantly diminished the fetal rejection rate and significantly reduced the numbers of splenic TH17 cells. Our results suggest that the peritoneum harbors two distinct B1a B cell subsets that can be distinguished by their PC1 expression. Whereas PC1(high) B1a B cells seem to support fetal survival, PC1(low) cells B1a B cells may compromise fetal well-being.
A Case of Thymic Carcinoma with Bone and Cerebral Metastases Treated with Stereotactic Radiosurgery and Chemotherapy
AMERICAN JOURNAL OF CASE REPORTS
Authors: Kropf, Jacqueline; Castaneira, Giselle; Luc, Lily T.; Oriala, Chukwuemeka; Field, Zachary; Rico, Alex; Carlan, Steve J.
Abstract
Objective: Unusual clinical course Background: Thymic carcinoma is a rare malignant neoplasm. High-grade thymic carcinoma has a high recurrence rate following surgery, and a low 5-year survival rate. Approximately 30% of patients with thymic carcinoma will be asymptomatic at the time of diagnosis. Extrathoracic metastasis on presentation is uncommon. Treatment of the primary tumor includes surgery, chemotherapy, and fractionated radiation. A rare case of thymic carcinoma that presented with bone and cerebral metastases is reported in a patient who responded well to stereotactic radiosurgery and chemotherapy. Case Report: A 63-year-old woman presented to the hospital for evaluation of hip pain. She was diagnosed with a lytic bone lesion of the right femur and brain metastasis. Biopsies from the mediastinal mass and right femur showed histological features consistent with carcinoma. Immunohistochemistry showed positive immunostaining of the tumor cells for the c-kit receptor (CD117) and CD5, supporting a diagnosis of stage IVb thymic carcinoma. Treatment included stereotactic radiosurgery, which delivered multiple radiation beams to the tumor tissue from different directions to target the tumor without affecting normal tissues. She was treated as an outpatient with carboplatin and taxol after stereotactic radiosurgery. The patient recovered well following treatment. Conclusion: A case of thymic carcinoma with bone and cerebral metastases was successfully treated with stereotactic radiosurgery and chemotherapy.