B cells require L-plastin for normal motility. In the absence of L-plastin, splenic maturation of B cells is impaired, with a loss of marginal zone B cells. Furthermore, germinal center B cell development is defective, with reduced humoral responses to model antigens. We are using lentiviral re-expression to perform the first structure-function analyses of L-plastin, to determine which regulatory elements are essential to L-plastin function. While the stated goal of these experiments is to determine which elements of L-plastin are required for B cell biology, we will also be analyzing other cell types. Furthermore, we have generated a floxed allele of L-plastin and will be using various Cre-promoters to analyze the B-cell specific requirement for L-plastin in germinal center responses.
We have also found that mice lacking L-plastin are exquisitely sensitive to lung infection with Streptococcus pneumoniae. This susceptibility correlates with a loss of alveolar macrophages, a unique lung-resident population of phagocytes essential to pulmonary innate immunity. We are currently completing a more thorough evaluation of the requirement for L-plastin in the development of alveolar macrophages, and establishing methodology to analyze in greater detail the changes in actin dynamics induced by loss of L-plastin.
Finally, we have a clinical-translational project analyzing whether variants in L-plastin or related genes may relate to increases susceptibility to invasive pneumococcal disease in patients. To provide context for this goal, we are also conducting a survey of pneumococcal carriage in the greater St. Louis area.
Techniques used in the lab include flow cytometry, confocal microscopy, live cell imaging, standard biochemical analyses (Westerns, immunoprecipitations), RT-PCR, ELISAs, and in vivo analyses of cellular immunology (adoptive transfers, generation of bone marrow chimeras, infectious models, etc). Whether your interest is microbiology, immunology, or at the intersection of host-pathogen biology, there is a project here for you!