Member, Fred Hutchinson Cancer Research Center
Professor of Medicine, Division of Rheumatology, University of Washington
The biological diversity of self: Microchimerism
Microchimerism (Mc) is harboring a small amount of cells or DNA that originated in another genetically distinct individual. Bi-directional maternal-fetal exchange occurs during normal pregnancy and creates a legacy of Mc in both individuals. Mc of maternal origin and, in women of fetal origin, is found in cells of the immune system including T and B lymphocytes, monocyte/macrophages, NK cells and granulocytes. Moreover, Mc is present as tissue-specific cells, for example cardiac myocytes, islet b cells, hepatocytes and other cell types. Mc has the potential for beneficial as well as adverse effects. A key variable is a complex of genes on the 6th chromosome that encode HLA molecules which are of central importance in immune responses. HLA genes are extraordinarily diverse and naturally acquired Mc therefore is usually about half similar and half dissimilar for HLA genes. In the autoimmune disease rheumatoid arthritis, for example, some types of Mc likely confer benefit and others confer risk depending upon the specific HLA alleles of the Mc as well as the HLA alleles of the person who harbors the Mc. In the setting of transplantation when donor and recipient differ for HLA there is a graft-versus-tumor benefit and a similar benefit has been implicated for Mc of fetal origin in immune surveillance against some types of cancer, especially breast cancer. Mc is present in healthy individuals and experimental studies point to benefits such as tissue repair and regeneration. Overall, naturally acquired Mc is common, diverse and durable pointing to a need for shift in perspective from the conventional self-versus-other paradigm to understanding the “self” as constitutively chimeric.
J. Lee Nelson, MD is a Member of the Fred Hutchinson Cancer Research Center and Professor of Medicine at the University of Washington. She heads a research group that has an overall goal of elucidating the beneficial and detrimental effects of maternal-fetal cell exchange during and subsequent to pregnancy. Dr. Nelson began her work focusing on immunological changes that occur during pregnancy and described fetal-maternal HLA-disparity in the pregnancy-induced amelioration of the autoimmune disease rheumatoid arthritis. She later spearheaded a new area of research examining the long-term consequences of naturally acquired microchimerism, with initial studies focused on systemic sclerosis, also called scleroderma. Microchimerism refers to harboring a small number of cells or DNA that originated in a genetically disparate individual. The most common microchimerism sources result from bi-directional maternal-fetal exchange during pregnancy - maternal cells that persist in her children into adult life and cells of fetal origin that persist in women who were previously pregnant. The research team she leads is interdisciplinary and studies microchimerism in autoimmune diseases, pregnancy complications, infectious disease, and cancer.