Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia : evidence of a subpopulation of protective anti-pneumococcal B1a cells

We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation‐induced cytidine deaminase (AID (−/−)), or invariant natural killer T (iNKT) cells (Jα18 (−/−)), or interleukin‐13 (IL‐13 (−/−)) had impaired early clearance of pneumococci in the lung, compared with wild‐type mice. In contrast, AID (−/−) mice adoptively transferred with AID (+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity‐like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen‐specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti‐pneumococcal B1a cell initiating response, probably through early production of IL‐13, given that IL‐13 (−/−) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID‐dependent subset

Natural killer cell memory in infection, inflammation and cancer

Immunological memory can be defined as a quantitatively and qualitatively enhanced immune response upon rechallenge. For natural killer (NK) cells, two main types of memory exist. First, similarly to T cells and B cells, NK cells can exert immunological memory after encounters with stimuli such as haptens or viruses, resulting in the generation of antigen-specific memory NK cells. Second, NK cells can remember inflammatory cytokine milieus that imprint long-lasting non-antigen-specific NK cell effector function. The basic concepts derived from studying NK cell memory provide new insights about innate immunity and could lead to novel strategies to improve treatments for infectious diseases and cancer