Marginal Zone B Cells Are Necessary for the Formation of Anti-donor IgG After Allogeneic Sensitization.

BACKGROUND: The formation of anti-major histocompatibility complex (MHC) antibodies is a significant barrier for many patients awaiting organ transplantation. Patients with preformed anti-MHC antibodies have limited options for suitable donors, and the formation of donor-specific anti-MHC antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-MHC antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigens are poorly understood. METHODS: To evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2 b C57Bl/6 sensitization with H-2 d antigen. We used a class I MHC tetramer-based approach to identify allogeneic B cells and flow cytometric crossmatch to identify allogeneic IgM and IgG. RESULTS: We found that although the formation of anti-H-2 d IgG was robust, few class-switched B cells and germinal center B cells were formed. Antigen-specific B cells did not express classical memory B-cell markers after sensitization but had an IgM + CD21 + marginal zone B-cell phenotype. The frequency of marginal zone B cells increased after sensitization. Depletion of marginal zone B cells before sensitization or skin grafting resulted in a significant diminution of anti-H-2 d IgG and fewer germinal center B cells. Adoptive transfer experiments revealed that marginal zone B cells more efficiently differentiated into germinal center B cells and anti-donor IgG-producing cells than follicular B cells. CONCLUSIONS: These results demonstrate an important role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigens.

Transplantation elicits a clonally diverse CD8+ T cell response that is comprised of potent CD43+ effectors.

CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ T cells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+ T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector T cells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ T cells have a distinct response profile relative to anti-pathogen CD8+ T cells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after transplantation.

Lemierre's Syndrome (LS) Complicated by Cranial Nerve XII Palsy.

Lemierre's syndrome (LS) is a rare medical condition that involves an acute oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein with embolic spread to organs like the kidneys, lungs, and large joints. Only very little literature has reported central nervous system involvement with LS. This is a case of 34-year-old woman with right-sided neck pain, swallowing difficulties, and a sore throat of 3 days duration at the time of presentation. CT of the neck with contrast showed a ruptured right peritonsillar abscess and thrombus in the right internal jugular vein suspicious of thrombophlebitis. The patient was managed for LS with IV antibiotics and anticoagulation. However, her clinical course was complicated by cranial nerve XII palsy, which is an extremely rare manifestation of LS.

A critical appraisal of COVID-19 as a nosocomial infection: an African perspective.

The pandemic of Coronavirus disease 19 is not abating since the outbreak began in December 2019. Africa is currently experiencing a surge after an initial low incidence and nosocomial infections could be contributing to this. A dominant factor responsible for this is a weak healthcare system because of many years of neglect due to abysmal budgetary allocation to the sector. The testing capacity for COVID-19 diagnosis in Africa is grossly inadequate coupled with a severe shortage of personal protective equipment and inadequate infectious diseases expert. These factors exposed the frontline health workers and patients to the hazard of nosocomial infection with the attendants´ morbidity and mortality. Deliberate efforts need to be made toward reducing nosocomial COVID-19 infection.

Inter-Lineage Variation of Lassa Virus Glycoprotein Epitopes: A Challenge to Lassa Virus Vaccine Development.

Lassa virus (LASV), which causes considerable morbidity and mortality annually, has a high genetic diversity across West Africa. LASV glycoprotein (GP) expresses this diversity, but most LASV vaccine candidates utilize only the Lineage IV LASV Josiah strain GP antigen as an immunogen and homologous challenge with Lineage IV LASV. In addition to the sequence variation amongst the LASV lineages, these lineages are also distinguished in their presentations. Inter-lineage variations within previously mapped B-cell and T-cell LASV GP epitopes and the breadth of protection in LASV vaccine/challenge studies were examined critically. Multiple alignments of the GP primary sequence of strains from each LASV lineage showed that LASV GP has diverging degrees of amino acid conservation within known epitopes among LASV lineages. Conformational B-cell epitopes spanning different sites in GP subunits were less impacted by LASV diversity. LASV GP diversity should influence the approach used for LASV vaccine design. Expression of LASV GP on viral vectors, especially in its prefusion configuration, has shown potential for protective LASV vaccines that can overcome LASV diversity. Advanced vaccine candidates should demonstrate efficacy against all LASV lineages for evidence of a pan-LASV vaccine.