A specialized subpopulation of the antibody-producing B cells of the immune system plays a "double-barreled" role in triggering both kinds of immunity - innate and acquired, Duke University Medical Center immunologists have discovered. The division of labor between B-1a and B-1b cells they have uncovered offers basic insights that could contribute to more rational development of vaccines, they said.
B cells are the arms factories of the immune system, producing antibodies that target invading microbes for destruction. Generally, B-1 cells have been thought to play a major role in the innate immune response - the type of immunity that offers rapid, generalized responses to infections. Less understood has been any role in adaptive immunity - in which the immune system develops a long-term immune response to an invader after vaccination or infection.
The researchers - Karen Haas, Jonathan Poe, Douglas Steeber and Thomas Tedder - published their findings in the July 2005 issue of the journal Immunity. The research was sponsored by the National Institutes of Health, the Arthritis Foundation, the Lymphoma Research Foundation and the Leukemia & Lymphoma Society.
The researchers studied a particular type of B cell called the B-1 cell. In contrast to the more conventional B-2 cells, B-1 cells have different distinguishing characteristics such as behavior, anatomical localization and types of antibodies produced. In contrast to well-studied B-2 cells, the cellular origins of B-1 cells and their subtypes remain unknown.
"The true function of B-1 cells in the body has been highly controversial over the past two decades," said Tedder. "They appear to be a primary defense mechanism for innate immunity in infections. In particular, however, the B-1b cells have been largely ignored because they're present in relatively small numbers and are difficult to work with."
In the studies, Haas and her colleagues used two genetically altered mouse strains - one that overproduced and one that was deficient in a protein called CD19 that is a key regulator of B-1a cell function and development. Thus, the two mouse strains enabled the researchers to explore the consequences of too many or too few B-1a cells. Also, the strain lacking CD19, and therefore B-1a cells, enabled the researchers to isolate sufficient numbers of pure B-1b cells for study.
The researchers studied how the immune systems of the two mouse strains reacted to infection with Streptococcus pneumoniae, the bacterium that causes pneumonia. They found that the mice lacking B-1a cells were susceptible to infection, showing they lacked the natural antibodies of the innate immune system. Yet, these mice could be protected by immunization, which activated their adaptive long-term immune system.
By contrast, the mice with overproduction of CD19 and thus overproduction of B-1a cells did not achieve adaptive immunity as a result of vaccination.
Thus, the researchers concluded that the B-1a cells regulate the innate immune response and the B-1b cells regulate the adaptive, long-term immune response.