When individuals are infected with HIV, they carry the virus for life. Inside their bodies, the virus is mutating and evolving and can develop into multiple separate strains. Because humans acquire HIV from other humans in whom this process is already taking place, the initial HIV virus sample that infects a susceptible healthy individual often already contains a variety of slightly different versions of the virus, accelerating virus diversification within the new patient. The diversity of HIV strains within a given individual represents one of several challenges the human immune system faces when attempting to battle HIV.
With other non-HIV infections, when the immune system learns to recognize the pathogen it can mobilize a swarm of cells with specificity for that pathogen to attack it and clear the infection. The diversity of HIV strains within a patient disrupts this process. Typically an HIV patient will develop an immune response that targets some but not all of the HIV strains present in the body those strains are dissimilar. One set of key molecules responsible for the “recognition” of pathogens are called antibodies. Many research efforts aspiring to develop an HIV vaccine or cure target the development of broadly-neutralizing antibodies (bnAbs), antibodies that recognize a wide range of HIV strains rather than only a subset of the strains present in an infected individual.
Research work published by Gao et al. in the July 2014 issue of Cell investigated the mechanisms that contribute to bnAb development in an HIV patient who naturally makes these antibodies. They found that two different populations of an immune cell type called a B cell participate in this process. Each B cell has a certain pathogen specificity and one key part of the immune response to an infection is the selective activation of B cells specific for pathogens the body is actively trying to fend off, which causes these B cells to mature into plasma cells that mass-produce antibodies with the same specificity as the B cells. Gao et al. found the B cells that produced bnAbs were activated because they were successful at recognizing a particular variant of the virus with a mutation in part of its surface called Loop D. These Loop D mutant viruses had been enriched in the population of HIV virus strains within this patient by a separate population of B cells that Gao et al. called the “helper B cells.” Having more of these Loop D mutants due to the activity of the helper B cells increased activation of bnAB B cells and therefore increased bnAb production. The helper B cells enriched the population of Loop D mutant HIV viruses because the Loop D mutants were resistant to the helper B cells. Because the helper B cells could not recognize the Loop D mutants, the Loop D HIV population survived while the helper B cells targeted other variants of HIV in the patient’s body. The activity of the helper B cells enriched the Loop D mutant population, which then activated the B cells that would mature into bnAb-producing plasma cells.
View the original publication here: http://www.cell.com/abstract/S0092-8674(14)00812-5
I also made this diagram to help clarify the process of bnAb development described in this paper: