Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Mature fetal B cell immunoglobulin gene expression profiles provide insights into the development of the fetal immune repertoire

Investigators: David Lawrence, Alexander Barron
Case Western Reserve University School of Medicine, Center for Global Health and Disease

Mentor: Christopher L. King, MD

Background: Antibodies derived from fetal cord blood represent an important component of the neonatal immune response. Though the antigen-naïve immature B cells which reside in the cord blood are well described in the literature, the antigen-exposed mature B cell population has not previously been examined.

Methods: Single, viable, IgG+, CD19+, fetal and adult mature B cells were isolated by fluorescence activated cell sorting and variable region gene segments for each cell were amplified and sequenced. The IMGT/V-Quest tool was utilized to identify the immunoglobulin heavy chain variable (V), diversity (D), and joining (J) segment gene family usage, degree of nucleotide addition and trimming at VDJ junctions, number of somatic hypermutations within the heavy chain variable (VH) region, and the total length of the most heterogeneous complementarity determining region (CDR), CDR3.

Results: Mature fetal B cells displayed a similar utilization of IGHD and IGHJ gene families, underwent a similar degree of nucleotide additions and trimming at the VDJ junctions, and displayed similar CDR3 lengths as their adult counterparts. However, mature fetal B cells displayed limited IGHV gene family diversity and underwent significantly fewer nonsynonymous somatic hypermutations within the VH region (1.0, range 0-3) when compared to adult mature B cells (10.4, range 3-15, P<0.0001).

Conclusions: Fetal mature B cells can generate a junctional diversity similar to adult mature B cells and display somatic hypermutation within the VH region, though at a significantly lower frequency than their adult counterparts.

Last Updated: 12/18/13

Updated on December 18, 2013.

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