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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.

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.

Influenza B virus (IBV) infections can cause severe disease in children and the elderly. Commonly used antivirals have lower clinical effectiveness against IBV compared to influenza A viruses (IAV). Neuraminidase (NA), the second major surface protein on the influenza virus, is emerging as a target of broadly protective antibodies that recognize the NA active site of IAVs. However, similarly broadly protective antibodies against IBV NA have not been identified. Here, we isolated and characterized human monoclonal antibodies (mAbs) that target IBV NA from an IBV-infected patient. Two mAbs displayed broad and potent capacity to inhibit IBV NA enzymatic activity, neutralize the virus in vitro, and protect against lethal IBV infection in mice in prophylactic and therapeutic settings. These mAbs inserted long CDR-H3 loops into the NA active site, engaging residues highly conserved amongst IBV NAs. These mAbs provide a blueprint for the development of improved vaccines and therapeutics against IBVs.

Pathogenic autoantibodies causing encephalopathy modify the expression of the glucose transporter in oligodendrocytes.

Autoantibodies that recognize the glycine receptor mediate pathology by directly interrupting glycinergic neurotransmission that manifests as a disorder characterized by muscle stiffness and spasms.

Pathogenic autoantibodies in neuromyelitis optica require antigen array assembly and a specific epitope to initiate robust complement activation.

Self-reactive T cells that traffic to the brain tissue of patients with multiple sclerosis are driven by antigen-experienced B cells.

Bats that harbor lethal viruses avoid disease through an evolved antiviral defense strategy that leverages tolerance for infections.

Viral exposure—the complete history In addition to causing illness, viruses leave indelible footprints behind, because infection permanently alters the immune system. Blood tests that detect antiviral antibodies can provide information about both past and present viral exposures. Typically, such tests measure only one virus at a time. Using a synthetic representation of all human viral peptides, Xu et al. developed a blood test that identifies antibodies against all known human viruses. They studied blood samples from nearly 600 people of differing ages and geographic locations and found that most had been exposed to about 10 viral species over their lifetime. Despite differences in the rates of exposure to specific viruses, the antibody responses in most individuals targeted the same viral epitopes. Science , this issue 10.1126/science.aaa0698