PHILADELPHIA - Steve Reiner, MD, professor of Medicine, and Burton Barnett, a doctoral student in the Reiner lab at the Perelman School of Medicine at the University of Pennsylvania, have shown how immune cells, called B lymphocytes, are able to produce daughter cells that are not equal, a finding that might explain how lifelong antibodies are made after vaccination.
How do immune cells make daughter cells that are different from one another, rather than splitting into identical daughter cells? The team’s paper, published this week online in Science, shows how one cell type can reliably produce cell diversity. Motile B cells that don’t have life-long attachments with other cells, as say a layer of skin cells do, can receive cues from other immune cells, namely helper T cells, so that they attach to each other and influence the outcome of B-cell division. The researchers showed that a T cell forms a temporary attachment to a B cell, which induces the B cell to divide, resulting in daughter cells that are different on the level of the proteins they inherit. The pairing and dividing occurs in the lymphoid organs, such as the spleen, that respond to vaccination.
B cells circulate throughout the body via the bloodstream, and upon infection are recruited to fight the offending germ. During this fight, the recruited B cells must generate multiple types of daughter cells to be effective. One of these cells makes the antibodies that destroy the germ, and are what make vaccinations effective. The other type of cell improves the quality of the antibodies that can be made.
The Penn team found that B cells segregate a transcriptional protein called Bcl6, the protein receptor for interleukin-21, and another protein called atypical PKC to one side of the plane of division during cell replication, generating unequal inheritance of fate-altering molecules by daughter cells. These three proteins tell the B cell which type of daughter cell to become; and by making daughter cells with more or less of these proteins, B cells can give rise to cells that are antibody factories through division.
The team is interested in using this discovery to make better vaccines. They are also expecting that the ability of wandering immune cells to give birth to non-identical daughters may explain how our blood cells can also turn into cancers like leukemia.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.