Immunology Select

Several recent studies use microscopy, mass spectroscopy, and proteomic analysis of B cells to elucidate the rapid changes that occur when the B cell receptor engages with its antigen. Other new findings call attention to the emerging role of Toll-like receptors in B cell-mediated autoimmunity. Here we discuss these studies and what they reveal about the intriguing biology of B cells. B cells are the antibody-producing cells of the mammalian immune system. The first step in antibody production is recognition by B cell receptors of foreign antigens expressed by target cells. Antigen recognition is followed by clustering of B cell receptors and their bound antigen; this cluster is then surrounded by a ring of adhesion molecules to form an immunological synapse. In an elegant mi-croscopy study, Fleire et al. (2006) now reveal the earliest steps in the formation of the B cell immunological synapse. First, they labeled the membranes of mouse B cells engineered to respond to hen egg lysozyme antigen with a lipid soluble red dye. Then they engineered target cells to express hen egg lysozyme tagged with green fluorescent protein. Using scanning electron microscopy and three-dimensional time-lapse fluorescence microscopy, the authors were able to observe the earliest steps after recognition of the lysozyme antigen by B cell receptors. First, the B cells spread over the membranes of target cells expressing the antigen within 2–4 min of contact; next the B cells contracted in a second phase lasting 5–7 min. This spreading-contraction response served to sweep antigen into a central cluster, a prerequisite for immunological synapse formation. This B cell response was dependent on: a specific interaction between the B cell receptor and hen egg lysozyme (because a mutant form of this antigen that lacks measurable affinity for the BCR did not elicit the response), activation of B cell receptor signaling, and actin polymerization. The authors then designed a computer model to describe in detail the spreading-contraction B cell response. This study sheds light on the earliest steps in the formation of the immunological synapse in B cells and provides an elegant model system with which to analyze the remarkable ability of B cells to discriminate antigen. A key step in the activation of B cells following recognition and binding of an-tigen is the phosphorylation of tyrosine residues in the cytoplasmic domains of the B cell receptor. The phosphorylation step is known to be carried out by a Src-family …