Dissecting human antibody responses: useful, basic and surprising findings

Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. Most surprisingly, this approach has also revealed a new mechanism of diversification based on templated insertion of non‐Ig DNA into antibody genes that we discovered in the context of the immune response to malaria infection

Cytokine-driven Proliferation and Differentiation of Human Naive, Central Memory, and Effector Memory CD4+ T Cells

Memory T lymphocytes proliferate in vivo in the absence of antigen maintaining a pool of central memory T cells (TCM) and effector memory T cells (TEM) with distinct effector function and homing capacity. We compared human CD4+ naive T, TCM, and TEM cells for their capacity to proliferate in response to cytokines, that have been implicated in T cell homeostasis. Interleukin (IL)-7 and IL-15 expanded with very high efficiency TEM, while TCM were less responsive and naive T cells failed to respond. Dendritic cells (DCs) and DC-derived cytokines allowed naive T cells to proliferate selectively in response to IL-4, and potently boosted the response of TCM to IL-7 and IL-15 by increasing the expression of the IL-2/IL-15Rβ and the common γ chain (γc). The extracellular signal regulated kinase and the p38 mitogen-activated protein (MAP) kinases were selectively required for TCR and cytokine-driven proliferation, respectively. Importantly, in cytokine-driven cultures, some of the proliferating TCM differentiated to TEM-like cells acquiring effector function and switching chemokine receptor expression from CCR7 to CCR5. The sustained antigen-independent generation of TEM from a pool of TCM cells provides a plausible mechanism for the maintenance of a polyclonal and functionally diverse repertoire of human CD4+ memory T cells