B-Cell Primary Immunodeficiency: What To Know

B cells are an important part of your immune system. In some forms of primary immunodeficiency (PI) — also called inborn errors of immunity (IEI) — B cells are missing or can’t do their job. Reduced or abnormal B cells can weaken your body’s ability to fight infections.

B-cell primary immunodeficiency disorders are among the most common PI conditions. Their impact on health and daily life can range from relatively mild to severe.

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 immune proteins known as antibodies. B cells are also called B lymphocytes.

Antibodies are proteins that can recognize and stick to antigens. Antigens are substances that trigger an immune response, such as proteins or other molecules found on 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.

Each antibody can recognize a specific part of an antigen, known as an epitope. In that way, it’s like a key that fits a specific 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 next time that germ enters your body, the B cells that remember it will quickly make antibodies. The infection will then clear faster.

This is one way vaccines work: They expose the immune system to an antigen so it can respond more quickly if it encounters the disease-causing germ later.

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 body will have B cells and antibodies ready to fight it.

What Are B-Cell Primary Immunodeficiency Disorders?

Primary immunodeficiency disorders are a large group of conditions, many of which are caused by genetic mutations (changes to your DNA).

All PI conditions affect some part of the immune response. Which cells or processes are involved depends on the underlying immune-system defect, which may involve one or more genetic changes. 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 T cells, another type of lymphocyte. One example of this is severe combined immunodeficiency (SCID). 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.

Agammaglobulinemia: Very Few B Cells, Very Few Antibodies

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 (GI or digestive) tract.

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

People with agammaglobulinemia should not get live vaccines. While these vaccines use weakened germs that are safe for most people, they can cause serious illness in anyone with a severely weak immune system.

Your healthcare provider can recommend which vaccines are safe and helpful to get depending on the severity of your condition.

CVID: Normal or Low B Cells, Very Few Antibodies

Common variable immunodeficiency (CVID), also called common variable immune deficiency, is one of the most common types of PI. CVID is usually diagnosed in adulthood. It’s estimated to affect between 1 in 25,000 and 1 in 50,000 people.

The cause of CVID is unknown in most cases. Identified genetic changes account for some cases, and symptoms can vary widely from person to person. Some of these conditions are named after the genes that cause them, such as CD19 deficiency.

People with CVID may be more likely to develop complications such as:

• Recurrent sinus or lung infections
• Low levels of antibody types IgG, IgA, and/or IgM
• Poor vaccine responses

Some people with CVID mainly experience frequent infections. About 25 percent to 50 percent of people with the condition also develop autoimmune or inflammatory problems. These complications occur when the immune system either mistakenly attacks healthy tissues or triggers chronic, uncontrolled inflammation throughout the body.

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

In this type of immunodeficiency, people have normal levels of B cells, but their B cells have trouble producing certain types of antibodies. Some people with hyper immunoglobulin M (HIGM) syndrome also have problems with T cells.

Antibodies are also called immunoglobulins (Igs), and they come in different classes, including:

• Immunoglobulin A (IgA)
• Immunoglobulin E (IgE)
• Immunoglobulin D (IgD)
• Immunoglobulin G (IgG)
• Immunoglobulin M (IgM)

Each type of antibody has different functions.

In hyper IgM syndrome, IgA and IgG levels 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
• Chronic diarrhea from GI tract infections
• Immune-related complications, such as inflammatory bowel disease-like enterocolitis or inflammatory arthritis

Normal B Cells, Selectively Low Antibodies

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. The prevalence of selective IgA deficiency varies widely among populations, with estimates ranging from about 1 in 143 to 1 in 18,500 people. About two-thirds of people with this condition have no symptoms.

When SIGAD symptoms do appear, they may include:

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

How Are B-Cell PI 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 — Measure 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 tests — Look for gene mutations that cause PI

How Are B-Cell PI 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:

• Practicing good hand-washing habits
• Staying up to date on vaccines, based on your healthcare providers’ recommendations, and ensuring that caregivers and close contacts are also vaccinated
• Taking extra precautions while traveling, such as drinking bottled water and avoiding raw or unwashed produce
• Using 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 certain severe B-cell PI conditions, newer treatments aim to fix the root problem rather than only replace antibodies. These include bone marrow transplants — which have been used successfully in select severe cases — and newer gene therapies that are currently being studied.

Because the use of these treatments is limited, immunoglobulin replacement remains the main treatment for many antibody deficiencies.

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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