Genomic engineering of B cells

​Description of Research

B lymphocyte development and function is controlled by a hierarchy and network of transcription factors including PU.1, Ikaros, Helios, Aiolos, E2A, EBF, Pax5, Bcl-6, IRF4, IRF8 and Bach2. The aim of our research project is to increase the understanding of the molecular and cellular mechanisms that regulate B cell differentiation into plasma cells. The ease of gene targeting and compactness of avian Ig light chain loci makes DT40 cells  also an ideal model  to investigate the molecular mechanisms of immunoglobulin gene  conversion and somatic hypermutation (SHM). Furthermore we have recently created a novel human Ramos B cell mutant lacking Bach2 gene expression using CRISPR-Cas9 gene targeting system. Currently we are analyzing the Bach2 deleted Ramos B cell phenotype by flowcytometry, RNAseq and CHIPSeq and comparing the results with two different DT40 Bach2 deleted mutants which have an opposite phenotype concerning the Ig gene conversion and maybe also SHM which we are studying using Green Fluorescent Protein (GFP)-loss assay system.

Members of the research group

Dr. Jukka Alinikula PhD, postdoc
Dr. Kalle-Pekka Nera PhD, postdoc
Dr. Minna Kyläniemi PhD, postdoc
MSc Paulina Budzynska, PhD student
BSc Anni Soikkeli, master student
Ann-Sofie Wierda, lab technician

Selected Publications

Nera KP,  Kohonen P, Veistinen E, Peippo A, Mustonen L, Terho P, Koskela K, Buerstedde J-M, Lassila O. Loss of Pax5 promotes plasma cell differentiation. Immunity 24(3): 283-93, 2006.

Alinikula J, Kohonen P, Nera KP, Lassila O. Concerted action of Helios and Ikaros controls the ex-pression of inositol 5-phosphatase SHIP. Eur J Immunol 40(9): 2599-607, 2010.

Alinikula J, Nera KP, Junttila S, Lassila O: Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation. Eur J Immunol 40, 2404-1413, 2011.

Buduzynska P, Niemelä M, Sarapulov A, Kyläniemi M, Nera KP, Junttila S,  Laiho A, Mattila P, Alinikula J, Lassila O: IRF4 deficiency leads to altered BCR signaling revealed by enhanced PI3K pathway, de-creased SHIP expression and defected cytoskeletal responses. Scand J Immunol 82, 418-428, 2015

Nera KP, Kyläniemi M, Lassila O: Regulation of B cell to plasma cell transition within the follicular B cell response. Scand J Immunol 82,225-34, 2015.