Most types of B cells return to normal levels within 12 months after starting antiretroviral therapy, leading to a partial—but incomplete—recovery of the immune system, say researchers of a new study published in the Journal of Infectious Diseases.

Much attention has been paid to CD4+ T cells in HIV disease, as they are the cells preferentially infected and destroyed by the virus. B cells are another important type of immune system cell, responsible for manufacturing antibodies, which target and help overcome most infectious diseases. And just as HIV negatively impacts populations of CD4 cells, it also damages B cell populations.

Like most immune system cells, not all B cells are alike. When we are first exposed to disease-causing microorganisms, often as children, some of the B cells created to fight a specific germ become inactivated and live on as resting “memory” cells. When exposed to the same infection again in the future, these memory B cells wake up and quickly mount an effective immune response. The cells that go out and actively engage in fighting the disease are called “activated” B cells. When B cells are first created, in what is called a naive state, they can become either activated B cells or memory B cells.

In untreated HIV disease, the proportion of the different types of B cells becomes uneven. The numbers of naive and memory cells become significantly depleted. As with CD4 cells, when these naive and memory cells become dangerously low, the body no longer “remembers” how to fight certain diseases, and people can become ill with the diseases known as opportunistic infections. Because there are few naive cells, the body can’t create enough new memory and activated cells to fight off new diseases either.

The number of activated B cells, however, increases significantly in untreated HIV disease. However, these cells are often dysfunctional and prone to apoptosis—cellular suicide (preprogrammed cell death).

Susan Moir, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, and her colleagues sought to determine whether antiretroviral therapy would cause the proportion of B cells to return to normal levels and thus signal a restoration of the immune system.

Moir’s team enrolled 29 HIV-positive people who were ready to start antiretroviral therapy. Eighty percent were men, and they were matched with 34 HIV-negative participants who served as a control group. Measurements of immune cells were taken at baseline—the start of the study—and at three, six and 12 months after the HIV-positive participants started antiretroviral thereapy.

Of the 29 HIV-positive participants, 24 ultimately had measurements of immune cells available from all time points. Moir’s team found that the number of B cells overall increased by the 12th month following the start of antiretroviral therapy. The percentage of the dysfunctional activated B cells dropped dramatically, while the percentage of naive and memory B cells increased, especially the naive cells.

Memory cells, however, only increased to 12 percent of the B cell population. This is significantly lower than the 40 percent seen in the HIV-negative participants.

The authors conclude that while antiretroviral therapy may help normalize immune regulation, it does not completely restore immune function. They question whether starting antiretrovirals earlier, before memory B cell populations become so depleted, may be warranted and encourage more research to understand the impact of earlier treatment.