T cell interactions with B cells during germinal center formation, a three‐step model

A Biram, N Davidzohn, Z Shulman - Immunological reviews, 2019 - Wiley Online Library
A Biram, N Davidzohn, Z Shulman
Immunological reviews, 2019Wiley Online Library
Establishment of effective immunity against invading microbes depends on continuous
generation of antibodies that facilitate pathogen clearance. Long‐lived plasma cells with the
capacity to produce high affinity antibodies evolve in germinal centers (GC s), where B cells
undergo somatic hypermutation and are subjected to affinity‐based selection. Here, we
focus on the cellular interactions that take place early in the antibody immune response
during GC colonization. Clones bearing B‐cell receptors with different affinities and …
Summary
Establishment of effective immunity against invading microbes depends on continuous generation of antibodies that facilitate pathogen clearance. Long‐lived plasma cells with the capacity to produce high affinity antibodies evolve in germinal centers (GCs), where B cells undergo somatic hypermutation and are subjected to affinity‐based selection. Here, we focus on the cellular interactions that take place early in the antibody immune response during GC colonization. Clones bearing B‐cell receptors with different affinities and specificities compete for entry to the GC, at the boundary between the B‐cell and T‐cell zones in lymphoid organs. During this process, B cells compete for interactions with T follicular helper cells, which provide selection signals required for differentiation into GC cells and antibody secreting cells. These cellular engagements are long‐lasting and depend on activation of adhesion molecules that support persistent interactions and promote transmission of signals between the cells. Here, we discuss how interactions between cognate T and B cells are primarily maintained by three types of molecular interactions: homophilic signaling lymphocytic activation molecule (SLAM) interactions, T‐cell receptor: peptide‐loaded major histocompatibility class II (pMHCII), and LFA‐1:ICAMs. These essential components support a three‐step process that controls clonal selection for entry into the antibody affinity maturation response in the GC, and establishment of long‐lasting antibody‐mediated immunity.
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