“Almost everyone has heard of antibodies,” says Parham Ramezani-Rad, Ph.D. “Far fewer people know about the cells that make them. I think of B cells as living sensors and learners.”
Most cells in the body do one job, one way, for life. B cells are different. Over the course of an immune response, B cells change their own antibody genes and compete with one another, and the immune system keeps the ones that work best. This is a kind of biological learning, and it happens inside us every time we fight an infection or get a vaccine.
Ramezani-Rad recently launched his own lab as a Research Assistant Professor at La Jolla Institute for Immunology (LJI). His lab seeks to understand the rules of that learning process: what makes one B cell response succeed and another fade. Those rules matter well beyond the lab bench because they shape how well vaccines protect us and how antibodies can be used to detect and treat infections, cancer, and other serious diseases.
Along the way, Ramezani-Rad hopes more people will come to appreciate the importance of B cells.
B cells are “living sensors”
B cells begin life in the bone marrow. As each one develops, it assembles a unique receptor—a molecular sensor on its surface—by shuffling and stitching together pieces of DNA in a partly random way. The result is that every B cell ends up recognizing a slightly different molecular shape.
No single B cell recognizes much. But the body carries billions of different B cells, and together they cover an astonishing range of shapes, including ones no human has ever encountered. Long before you meet a particular virus, a few of your B cells are already able to see a piece of it.
But simply recognizing a threat isn’t enough. The antibodies a B cell can make on first contact are usually a loose fit—good enough to help but rarely good enough to finish the job. The immune system’s real trick is improving on that first rough draft.
Inside the immune system’s training grounds
When an infection takes hold—or a vaccine arrives—pieces of the intruder are carried to lymph nodes, small filtering organs seeded throughout the body. B cells that recognize those pieces are activated, and with the help from other immune cells, they gather to build temporary structures called germinal centers.
A germinal center is part workshop, part audition. As the B cells inside divide, they make small, random changes to their own receptors. Most of those changes are useless, but few changes produce a better fit between a receptor and a target on the invading pathogen.
Then the cells are put to the test. Soon a germinal center holds thousands of related B cells, each with a slightly different receptor, all competing to recognize the same target. The ones that grip the target most tightly are selected to divide and change again. The rest drop out.
Round after round, the surviving B cells get better at recognizing the target. The winners graduate into two kinds of specialists: plasma cells, which produce large amounts of antibodies, and memory B cells, which stand by to restart the immune response quickly if the same threat ever returns—even years later.
Antibodies go to work
Antibodies are the other little miracle in this story. An antibody is essentially a free-floating copy of the receptor a B cell used to recognize its target. Once a B cell has refined its sensor, it can secrete that same shape by the millions.
Imagine if any other part of the body worked like that. Imagine if you could spit out extra hands to do jobs around the house.
These antibodies protect us in several ways at once. They can coat a virus so it can no longer get into our cells, clump pathogens together to slow their spread, and flag invaders so other immune cells can destroy them.
But the system does not always win. HIV, for example, has evolved to be a hard target: it hides its most vulnerable spots, and mutates so quickly that antibodies are often chasing a version of the virus that no longer exists.
“Every immune response is a series of decisions,” says Ramezani-Rad. “I want to understand the rules that determine which B cells succeed, which are lost, and ultimately which antibodies are made.”
Fundamental science guides vaccine innovation
Ramezani-Rad has spent his career on B cells in both health and disease. As a graduate student, he studied B cell leukemia, a type of blood cancer where abnormal B cells crowd out healthy cells in a person’s bone marrow, blood, and lymph nodes.
Since then, he has focused on how B cells generate protective antibody responses against difficult viruses such as HIV and influenza. In a 2025 Science Translational Medicine study, Ramezani-Rad and his collaborators showed that an experimental vaccine could steer B cells to make HIV-targeting antibodies in an animal model.
The new Rad Lab has its eye on vaccine innovation. Ramezani-Rad has funding through the National Institutes of Health to study how mRNA vaccines shape B cell learning and what it would take to build long-lasting immunity against HIV.
“There is real promise in newer technologies like mRNA vaccines,” he says. “But the vaccine is only the beginning. What matters is what the B cells do with it.”
