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Patients with autoimmune disease have exhausted antigen-specific T cells that remain capable of B cell support.

Whole-proteome autoantibody profiling reveals an immunological signature that predates the clinical onset of multiple sclerosis.

Curated expression of proteolipid protein 1 (PLP1) is essential for multiple sclerosis-derived autoantibody recognition.

Tissue-resident memory T cells accumulate in mucosal sites during infancy and then mature through childhood.

An approach for identifying antibodies derived from distinct B cell populations demonstrates how secondary immunization responses are dominated by mature B cells generated during primary responses.

Patients with multiple sclerosis display broad EBV-specific TCR repertoires driven by an enduring anti-EBV immune response.

T cells can acquire CD20 from B cells via trogocytosis, then contribute to autoimmune neurological disease while becoming targets for therapeutically effective B cell depletion.

Epileptic seizures can be mediated by patient autoantibodies targeting ion channels expressed in the brain.

Elevated frequency of afucosylated IgG1 antibodies during dengue virus infection is associated with prior infection and predicts severe disease., (Copyright © 2021, American Association for the Advancement of Science.)

Charting the gene-expression landscape of glioma-infiltrating T cells demonstrates that these T cells can express NK cell receptors, which inhibit the killing of glioma cells., (Copyright © , American Association for the Advancement of Science.)

Pathogenic autoantibodies causing encephalopathy modify the expression of the glucose transporter in oligodendrocytes., (Copyright © , American Association for the Advancement of Science.)

IgA-expressing antibody secreting cells that are formed in the gut travel to the brain to diminish inflammation during multiple sclerosis exacerbations., (Copyright © 2019, American Association for the Advancement of Science.)

Self-reactive T cells that traffic to the brain tissue of patients with multiple sclerosis are driven by antigen-experienced B cells., (Copyright © 2018, American Association for the Advancement of Science.)

Bats that harbor lethal viruses avoid disease through an evolved antiviral defense strategy that leverages tolerance for infections., (Copyright © 2018, American Association for the Advancement of Science.)

The human virome plays important roles in health and immunity. However, current methods for detecting viral infections and antiviral responses have limited throughput and coverage. Here, we present VirScan, a high-throughput method to comprehensively analyze antiviral antibodies using immunoprecipitation and massively parallel DNA sequencing of a bacteriophage library displaying proteome-wide peptides from all human viruses. We assayed over 10(8) antibody-peptide interactions in 569 humans across four continents, nearly doubling the number of previously established viral epitopes. We detected antibodies to an average of 10 viral species per person and 84 species in at least two individuals. Although rates of specific virus exposure were heterogeneous across populations, antibody responses targeted strongly conserved "public epitopes" for each virus, suggesting that they may elicit highly similar antibodies. VirScan is a powerful approach for studying interactions between the virome and the immune system., (Copyright © 2015, American Association for the Advancement of Science.)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinity maturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS., (Copyright © 2014, American Association for the Advancement of Science.)