The otherness of self: microchimerism in health and disease

Abstract

Microchimerism (Mc) refers to the harboring of a small number of cells (or DNA) that originated in a different individual. Naturally acquired Mc derives primarily from maternal cells in her progeny, or cells of fetal origin in women. Both maternal and fetal Mc are detected in hematopoietic cells including T and B cells, monocyte/macrophages, natural killer (NK) cells and granulocytes. Mc appears also to generate cells such as myocytes, hepatocytes, islet β cells and neurons. Here, the detrimental and beneficial potential of Mc is examined. The prevalence, diversity and durability of naturally acquired Mc, including in healthy individuals, indicates that a shift is needed from the conventional paradigm of 'self versus other' to a view of the normal 'self' as constitutively chimeric.

Figure 1

The four types of HLA-relationships of a mother and child are illustrated in Figure 1A. In the example, in column 1 there is bi-directional HLA incompatibility. In column 2 the child is HLA-identical to the mother resulting in bi-directional HLA compatibility. In column 3 the child inherited the same HLA allele from the father as the mother (homozygosity), which results in uni-directionally compatibility from the mother’s perspective with incompatibility from the child’s perspective. Similarly if the mother is homozygous the reverse is true (column 4). HLA-compatibility that results from HLA-identity or HLA-homozygosity has been hypothesized to contribute to some autoimmune diseases in which Mc is implicated [2,48]. Women can acquire Mc from their mother and from the fetus during their own reproductive life, thus becoming a recipient to Mc across generations. Although most of the time these different sources of Mc will differ for HLA alleles, the child’s paternally-inherited HLA allele could be the same as the HLA allele that was not transmitted from the grandmother to the child’s mother as illustrated in Figure 1B, column 2. Whether these types of familial HLA-relationships could predispose to autoimmunity is currently not known but is a subject of interest for future studies.

Figure 2

Naturally-acquired Mc has been identified in organs as multiple different types of differentiated cells and within a variety of hematopoietic cell lineages in humans. Maternal Mc and fetal origin Mc in women are the most common Mc sources. Hematopoietic Mc is found in individuals who are otherwise healthy, and differentiated cells in tissues have also been described in the absence of disease. These observations indicate naturally acquired Mc is likely an integral aspect of “the self,” with lifetime consequences sometimes for better and others times for worse.