{"id":1451,"date":"2026-03-06T09:39:18","date_gmt":"2026-03-06T08:39:18","guid":{"rendered":"https:\/\/bdagroup.nl\/?post_type=internship&#038;p=1451"},"modified":"2026-05-18T16:13:35","modified_gmt":"2026-05-18T14:13:35","slug":"analysis-of-igg4-class-switching-upon-repetitive-antigen-exposure-using-multi-omics-single-cell-analysis-of-antigen-specific-b-cells","status":"publish","type":"internship","link":"https:\/\/bdagroup.nl\/?internship=analysis-of-igg4-class-switching-upon-repetitive-antigen-exposure-using-multi-omics-single-cell-analysis-of-antigen-specific-b-cells","title":{"rendered":"ANALYSIS OF IgG4 CLASS SWITCHING UPON REPETITIVE ANTIGEN EXPOSURE USING MULTI-OMICS SINGLE-CELL ANALYSIS OF ANTIGEN SPECIFIC B CELLS"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">The generation of long-lasting high affinity antibodies is one of the core pillars of our immune system ensuring life-long protection against infection. Dysregulation of this process can cause severe pathological conditions, such as alloimmunization during blood transfusions or self-reactivity in auto-immune disease. &nbsp;High affinity antibodies are formed as product of a <em>germinal center<\/em> (GC) reaction, in which activated B cells proliferate and differentiated into antibodies-secreting cells (ASC). Understanding the exact mechanisms controlling this process within the GC is fundamental to devise strategies to modulate antibodies formation in both health and disease<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">During the past Sars-CoV2 pandemic we had the unique opportunity to investigate B cell differentiation dynamics in human settings by specifically analyzing Sars-CoV2 spike-specific B cells isolated from infected individuals or individuals undergoing mRNA vaccination. In particular, we generated a multi-omics single-cell dataset containing more than 40\u2019000 spike-specific B cells from 24 individuals at three timepoints after vaccination of which we analyzed transcriptome, surface protein expression and B-cell receptor (BCR) sequence.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In this project we will use our multi-omics single cell dataset to analyze IgG4 antibodies class switching upon repetitive antigen exposure. Antibodies produced by ASC come in different classes (IgD, IgM, IgG, IgA, IgE) and subclasses (for example IgG1, IgG2, IgA1, etc), each with distinct functional roles in immune responses. Antibodies can switch from a class (or subclass) to another by rearranging their structure, a process called \u201cclass switching\u201d. IgG4 is a subclass of IgG antibodies, which is defined as the tolerance antibody as it is induces upon repetitive antigen exposure and, contrary to other IgG subclasses antibodies, dampens down inflammatory responses. Yet, the exact mechanism leading to the production of IgG4 antibodies are still poorly defined. Upon Sars-CoV2 vaccination, IgG4 antibodies have been shown to develop after the 3<sup>rd<\/sup> injection in healthy individuals, but not in patients under the immunosuppressive drugs of the TNF inhibitors family. This suggest that TNF might play a role in IgG4 class-switching mechanisms. &nbsp;<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Your task within this project will be to characterize IgG4 producing cells in our spike-specific B cells and compare them between healthy individuals and patients under TNF inhibitors treatment. Additionally, you will apply a recently published algorithm called <em>sciCSR<\/em> to predict IgG4 class switching from single-cell transcriptomic data. Knowledge of R\/Phyton\/bash is required.<\/p>\n","protected":false},"template":"","categories":[],"tags":[],"class_list":["post-1451","internship","type-internship","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/internship\/1451","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/internship"}],"about":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=\/wp\/v2\/types\/internship"}],"wp:attachment":[{"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1451"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1451"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bdagroup.nl\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1451"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}