Does It Matter Which Arm You Use for a Booster Shot?

The Role of Memory B Cells

Vaccination protects against infection by inducing the production of neutralizing antibodies by plasma cells, as well as the formation of memory B cells. Long-lived plasma cells are terminally differentiated and produce antibodies with a fixed specificity and affinity to the original antigen.

In contrast, memory B cells can quickly differentiate into short-lived plasma cells in the lymph node (a process occurring in the subcapsular sinus at the surface of the node) or enter the germinal center, where their receptors undergo further diversification. This increases affinity to the original antigen and expands specificity to antigenic variants.

Australian researchers studied the fate of memory B cells after administering a booster dose. They confirmed previous suggestions that the immune response is stronger when the booster is given in the same arm as the initial dose—and they offered a likely explanation why.

Where Do Memory Cells Go?

The study demonstrated that memory B lymphocytes generated after the first immunization remain in the draining lymph nodes near the injection site. They are located in the subcapsular sinus, where they interact closely with macrophages that are primed to respond to pathogens.

These macrophages are already in a state of readiness, and when they capture an antigen, they immediately activate memory B cells—leading to the production of high-quality antibodies. These lymph-node-resident macrophages play a crucial role in orchestrating the most efficient immune response after a booster dose. The immune system, it seems, self-organizes in a way that enhances readiness for future threats.

Prof. Václav Hořejší from the Institute of Molecular Genetics of the Czech Academy of Sciences commented: “The published results make sense—this is just confirmation of what we have already intuitively assumed.”

A Step Toward Faster Herd Immunity

The effect was first demonstrated in mice and later confirmed in humans. The study involved 30 volunteers who received two doses of the BioNTech mRNA COVID-19 vaccine three weeks apart. Two-thirds received both shots in the same arm, while the rest got the second shot in the opposite arm.

The group that received both doses in the same arm showed significantly higher production of neutralizing antibodies within 5–7 days after the second dose. In the other group, the immune response was slower. After four weeks, both groups had similar antibody levels.

Vaccination in the same arm also produced higher early neutralizing antibody levels against COVID-19 delta and omicron variants. This early protection could be crucial during a rapidly spreading pandemic, helping accelerate herd immunity—especially important for rapidly mutating viruses.

A Study with a Small Sample Size

A limitation of the study is its small sample size. Other research has even shown potential benefits from alternating arms. Therefore, these findings need further validation through larger-scale studies and discussion within the immunology and vaccination communities.

Dr. Daniel Dražan, a board member of the Czech Vaccinology Society, noted that the topic was discussed during the COVID-19 pandemic but is currently not a priority issue within expert circles.

Editorial Team, Medscope.pro

Sources:

• Dhenni R., Hoppé A. C., Reynaldi A. et al. Macrophages direct location-dependent recall of B cell memory to vaccination. Cell 2025 Jun 26; 188(13): 3477–3496.e22, doi: 10.1016/j.cell.2025.04.005.
• Garvan Institute of Medical Research. Left or right arm? New research reveals why vaccination site matters for immune response. EurekAlert! 2025 Apr 28. Link to article