B-Cell Primary Immunodeficiency: What To Know

B cells are an important part of your immune system. In some forms of primary immunodeficiency (PI), B cells are missing or can’t do their job normally. This can weaken your body’s ability to fight infections.

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B-cell PI disorders are among the most common PI conditions. They can be diagnosed at any age, and their impact on health and daily life can range from severe to relatively mild. In this article, we’ll cover what causes B-cell PI conditions and discuss diagnosis and treatment options.

What Are B Cells?

B cells are a type of white blood cell that makes antibodies. They’re also called B lymphocytes. Antibodies are proteins that can recognize and stick to antigens — harmful substances that enter your body, such as viruses and bacteria. Antibodies help fight infections by sticking to germs and tagging them for destruction by other immune cells. When B cells are missing or can’t make antibodies, it’s harder for your body to fight infections.

In general, each antibody can recognize and stick to just one specific antigen — like a key that fits a particular lock. B cells and antibodies also serve as your immune system’s memory. If the same germ infects you again, your body will “remember” it. The B cells that make the specific antibody will quickly make more, and the infection will clear faster. This is how vaccines work. For example, when you get the flu vaccine, your body makes antibodies to parts of the flu virus. Later, if you’re exposed to the actual flu virus, your immune system will have B cells and antibodies ready to fight it.

What Are B-Cell Primary Immunodeficiency Disorders?

PI disorders are a large group of inherited conditions caused by genetic mutations (changes). Doctors may also call these conditions “inborn errors of immunity” (IEI), a newer term with the same meaning.

All PI conditions affect some part of the immune response. Which cells or processes are involved depends on which gene is mutated. B-cell PI conditions — those that mostly affect B cells and antibody production — make up 50 percent to 60 percent of all diagnosed PI conditions.

There are many kinds of PI conditions. Some affect both B cells and another type of white blood cell called T cells. One example of this is severe combined immunodeficiency. These combined conditions fall into a different category and won’t be covered here.

Below, we describe the different types of B-cell PI disorders.

Very Few B Cells, Very Few Antibodies: Agammaglobulinemia

This group includes the most severe forms of B-cell PI. People with agammaglobulinemia have very few or no B cells. As a result, they have very low levels of antibodies. One example is called X-linked agammaglobulinemia.

People with agammaglobulinemia tend to get serious bacterial infections, often over and over. These infections usually affect mucosal surfaces — moist areas of the body that act as the first barrier against germs. These areas include the respiratory tract (sinuses and lungs) and the gastrointestinal (digestive) tract.

The bacteria that cause these infections are often encapsulated, meaning they have a protective outer coating. Two common types are Haemophilus influenzae and Streptococcus pneumoniae.

People with agammaglobulinemia should not receive live vaccines. These vaccines contain weakened versions of germs that are usually safe, but they can cause infections in people with very low immune function.

Normal or Low B Cells, Very Few Antibodies: Common Variable Immunodeficiency and Similar Conditions

This group includes common variable immunodeficiency (CVID), which is one of the most common types of PI. CVID is usually diagnosed in adulthood, and it’s estimated to affect between 1 in 25,000 and 1 in 50,000 people. CVID can be caused by different gene mutations, which is why symptoms can vary from person to person. Some of these conditions are named after the genes that cause them, such as CD19 deficiency.

People with these conditions often get repeated infections, especially in mucosal surfaces, but they’re also at higher risk of many more viral infections than people with other types of B-cell PI. In addition, about 25 percent to 50 percent of people with CVID-like conditions develop autoimmune diseases — when the immune system mistakenly attacks the body’s own tissues.

Normal B Cells, Low IgG and IgA Antibodies: Hyper IgM Syndrome

In this type of B-cell PI, people have normal levels of B cells, but their B cells have trouble producing certain types of antibodies. Antibodies are also called immunoglobulins (Igs), and they come in different classes, including IgG, IgA, IgE, IgD, and IgM. Each type helps fight off different kinds of infections.

In hyper IgM syndrome, levels of IgG and IgA are low, while IgM is normal or high. Several rare gene changes can cause this condition. Some specific types include AID deficiency, UNG deficiency, and CD40 or CD40L deficiency.

Symptoms of hyper IgM syndromes are similar to those of other B-cell PI conditions and may include:

• Recurrent bacterial infections (repeated illness)
• Chronic diarrhea from digestive tract infections
• Immune-related complications, such as inflammatory bowel disease-like enterocolitis or inflammatory arthritis

Normal B Cells, Antibody Function Problems

This group includes B-cell PI conditions in which specific antibodies are missing or can’t function normally. The mutations that cause these conditions are often unknown. Examples include IgG subclass deficiency and selective IgA deficiency.

Symptoms vary widely. Many people with these conditions don’t notice any symptoms — they’re considered asymptomatic. For example, selective IgA deficiency is one of the most common antibody deficiency PI disorders, affecting up to 1 in 143 people in some ethnic groups. However, about two-thirds of people with this condition have no symptoms. When symptoms do appear, they may include:

• Frequent respiratory infections
• Digestive tract infections
• Lowered ability to make antibodies for specific antigens

How Are B-Cell Primary Immunodeficiency Conditions Diagnosed?

Like other PI diseases, B-cell PI conditions are diagnosed with laboratory tests. Many people first see a healthcare provider because they have frequent or severe infections. A family history of immune disorders can also be an important clue.

To see what’s going on with your immune system, your doctors may order tests such as:

• A complete blood count — Gives an overview of all types of cells in the blood
• Lymphocyte panels — Measures levels of specific white blood cells
• Immunoglobulin tests — Show levels of antibody classes (such as IgG, IgA, and IgM) in the blood
• Antibody function tests — Check how well the body responds to different antigens
• Genetic screening — Looks for gene mutations that cause PI disorders

How Are B-Cell Primary Immunodeficiency Disorders Treated?

The main goal of treating B-cell PI conditions is to prevent and manage infections. The exact type of treatment depends on how severe your condition is. Treatment mainly includes infection prevention and, in some cases, antibody replacement.

Infection Prevention

Because B-cell PI conditions raise the risk of infections, prevention is an important part of daily life. Preventive steps may include:

• Practice good handwashing habits.
• Stay up to date on vaccines, based on your healthcare providers’ recommendations, and ensure that caregivers and close contacts are also vaccinated.
• Take extra precautions while traveling, such as drinking bottled water and avoiding raw or unwashed produce.
• Use prophylactic (preventive) antimicrobial drugs, if prescribed by your doctor.

Immunoglobulin Replacement Therapy

In immunoglobulin replacement therapy, people with low levels of IgG receive extra antibodies from healthy blood donors. This treatment is commonly used for conditions such as agammaglobulinemia and CVID.

To prepare the treatment, the plasma (the liquid part of blood) from thousands of donors is combined. This pooled plasma contains antibodies against many different germs. However, these extra antibodies stay in the bloodstream for only a few weeks. Because immunoglobulin therapy replaces missing antibodies but doesn’t fix the immune problem itself, most people need to keep getting treatment for the rest of their lives.

For some of the most severe B-cell PI conditions, newer treatments aim to fix the root problem rather than only replace antibodies. These include bone marrow (stem cell) transplants and gene therapy, which are already being studied or used in certain cases.

If you have questions about your diagnosis or treatment, your healthcare provider is the best resource. They’ll know your medical history and best understand your specific condition.

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