title: IgM Repertoire Biodiversity is Reduced in HIV-1 Infection and Systemic Lupus Erythematosus.
abstract: BACKGROUND
  HIV-1 infection or systemic lupus erythematosus (SLE) disrupt B cell homeostasis, reduce memory B cells, and impair function of IgG and IgM antibodies.
  
  
  OBJECTIVE
  To determine how disturbances in B cell populations producing polyclonal antibodies relate to the IgM repertoire, the IgM transcriptome in health and disease was explored at the complementarity determining region 3 (CDRH3) sequence level.
  
  
  METHODS
  454-deep pyrosequencing in combination with a novel analysis pipeline was applied to define populations of IGHM CDRH3 sequences based on absence or presence of somatic hypermutations (SHM) in peripheral blood B cells.
  
  
  RESULTS
  HIV or SLE subjects have reduced biodiversity within their IGHM transcriptome compared to healthy subjects, mainly due to a significant decrease in the number of unique combinations of alleles, although recombination machinery was intact. While major differences between sequences without or with SHM occurred among all groups, IGHD and IGHJ allele use, CDRH3 length distribution, or generation of SHM were similar among study cohorts. Antiretroviral therapy failed to normalize IGHM biodiversity in HIV-infected individuals. All subjects had a low frequency of allelic combinations within the IGHM repertoire similar to known broadly neutralizing HIV-1 antibodies.
  
  
  CONCLUSIONS
  Polyclonal expansion would decrease overall IgM biodiversity independent of other mechanisms for development of the B cell repertoire. Applying deep sequencing as a strategy to follow development of the IgM repertoire in health and disease provides a novel molecular assessment of multiple points along the B cell differentiation pathway that is highly sensitive for detecting perturbations within the repertoire at the population level.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL , USA ; Florida Center for AIDS Research, University of Florida , Gainesville, FL , USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Cai
authors.forename: Mark Andrew
authors.initials: MA
authors.lastname: Wallet
authors.forename: Brent Paul
authors.initials: BP
authors.lastname: Gardner
authors.forename: Kaifen
authors.initials: K
authors.lastname: Chang
authors.forename: Amanda Catherine
authors.initials: AC
authors.lastname: Lowe
authors.forename: Carina Adriana
authors.initials: CA
authors.lastname: Rodriguez
authors.forename: Panida
authors.initials: P
authors.lastname: Sriaroon
authors.forename: William George
authors.initials: WG
authors.lastname: Farmerie
authors.forename: John William
authors.initials: JW
authors.lastname: Sleasman
authors.forename: Maureen Michels
authors.initials: MM
authors.lastname: Goodenow
keywords: HIV-1; IgM antibody transcriptome repertoire; IgM memory B cells; biodiversity; naïve B cells; pyrosequencing; somatic hypermutation; systemic lupus erythematosus