Environmental Factor

September 2011

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Fellow wins WSA award for research excellence

By Archana Dhasarathy
September 2011

Anne Lai, Ph.D.

Lai said the WSA award came as a very pleasant surprise. (Photo courtesy of Steve McCaw)

Postdoctoral fellow Anne Lai, Ph.D., has been selected to receive one of two NIH WSA (Women Scientist Advisors Committee)(https://sigs.nih.gov/wsa/Pages/default.aspx) Exit NIEHS Scholar Awards. Her abstract(https://www.niehs.nih.gov/news/newsletter/2011/august/spotlight-farewell/niehs-fare-abstracts.pdf), titled “DNA methylation primes the memory B cell epigenome for plasma cell differentiation,” was selected from a pool of all 2012 female FARE (Fellows Award for Research Excellence)(https://felcom.od.nih.gov/subCommittee/fare.aspx) Exit NIEHS award winners, by a panel of WSA representatives from across the NIH. This is the second year for the award.

Lai is currently an Intramural Research and Training Award (IRTA) fellow in the NIEHS Laboratory of Molecular Carcinogenesis Eukaryotic Transcriptional Regulation Group(https://www.niehs.nih.gov/research/atniehs/labs/lmc/etr/staff.cfm), headed by Paul Wade, Ph.D.(https://www.niehs.nih.gov/research/atniehs/labs/lmc/etr/index.cfm) An immunologist by training, Lai successfully applied her knowledge of the immune system towards deciphering the role of epigenetics in the adaptive immune response.

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The adaptive immune response

When naïve B cells in the blood encounter a foreign antigen, they respond by active mutation of their antibody-encoding DNA. These mature B cells, now referred to as activated B cells, can then differentiate into a vast number of antibody-secreting plasma cells in specialized structures called germinal centers. The antibodies generated by the plasma cells, which are specific to the invading antigen, help the body launch a counter attack.

In addition to plasma cells, activated B cells can also differentiate into memory B cells, which can more efficiently transition into plasma cells. Memory cells can thus recognize and mount a superior immune response against the same antigen if it is encountered in the future.

Several studies in the past have speculated that epigenetic changes could play important roles in functionally distinguishing the memory cells and naïve B cells from each other. One such epigenetic modification involves DNA methylation, or the addition of a methyl group to the cytosine of a cytosine-guanine (CG) pair in the DNA, which is generally associated with gene silencing.

Epigenetic signatures contribute to the immune response

Lai and colleagues used a genome-wide approach to examine the role of DNA methylation in the adaptive immune response. They purified four different human B cell subsets (naïve, mature, plasma, and memory B cells), representing stages of the immune response before and after antigen exposure, from human tonsils. DNA microarrays were then used to query these cells for differences in their DNA methylation and gene expression profiles.

They found widespread DNA methylation changes between naive and memory B cells, many of which were enriched near immune response genes, implying that DNA methylation was functionally relevant at these genes. This was interesting, because the gene expression profiles of these B cell subtypes are remarkably similar. In contrast, there were fewer differences in DNA methylation between memory B cells and plasma cells, despite their vastly different gene expression programs. The epigenetic differences between naïve and memory B cells may partially explain why memory B cells are more efficient in differentiating into plasma cells.

“Anne's work is significant, because immunologists have long suspected that epigenetics plays an important role in immunologic memory, and there is evidence to support this in T cells.  Anne's work provides an indication that this is likely to be the case for B lymphocytes as well,” said Wade.

Lai will be presented with a plaque and an award ribbon for her poster during the NIH Research Festival FARE awards ceremony this October.

(Archana Dhasarathy, Ph.D., is a postdoctoral fellow in the Eukaryotic Transcriptional Regulation Group in the NIEHS Laboratory of Molecular Carcinogenesis.)

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