B cell development stages Explained in a Simple Way

B cell development Stages Elaborated

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Understanding the B cell development stages is an important aspect of learning about humoral immunity. The B cells are the mediators of humoral immunity. Humoral immunity is part of the adaptive immune system which is the acquired immunity that protects you.

Therefore, it is critical to know the process that ultimately gives rise to functional B cells. The B cells play a vital role in protecting you against foreign attackers.

A highlight of the Vital Processes During the 7 B cell Development Stages

It is important that we try to highlight what goes on through the seven stages of B cell development before your body has mature functional B cells. The goal of this whole process is to have a mature B cell (Stage 7) that has all the necessary “tools” needed to recognize and fight an attacker (Microorganisms).

The most important marker that a mature B cell must have, is the B cell receptor (BCR) on its surface. This is what your B cells use to interact with the outside world of microorganisms and other antigens (e.g tumors, allergens).

During the seven stages, there are re-arrangements of several gene segments including the H-chains, L-chains, and V(D)J. As the rearrangement of these genes progresses the B cells continue to take form towards maturity.

The 7 Stages of B cell development

We shall now discuss the seven B cell development stages here.  Beginning with the most primitive stage we shall walk through to the most advanced that gives rise to the mature B cells.  The mature functional B cells protect you as part of the adaptive immune system.

1. Stem cell

This is the first stage of B cell development. These cells are so primitive that you can hardly tell (at this point) what they are going to become once they mature. Their H-chain genes and L-chain genes are encoded in the germline which means that they are heritable.

Look at the table below where B cells development stages are summarized. You can learn about all the characteristics of B cell stem cells by scanning across the row labeled serial number 1.

These cells do not express RAG/RdT, surrogate L-chain, and αβ immunoglobulin chains. The B cell stem cells only express the CD34 marker.  

2. Early Pro-B cell

This stage is the second stage of B cell development. The V and J gene segments start joining here. Several proteins are expressed in this stage before the most advanced form of the early pro-B cell expresses CD34, CD45/B220, and MHC Class II.

You can see more details about the markers associated with the early pro-B cell stage. Scan across the row number in the last cell on the extreme left of the summary table in this article. 

3. Late Pro-B cell

The 3rd stage of the B cell development is certainly superior to the 2nd stage in terms of the B cell taking shape and form towards maturity. Several markers are expressed on the plasma membrane surface of your developing B cells at this stage.

These markers include CD45R, MCH Class II, CD19, and CD40. For further details about all the features of this stage see across the row labeled serial number 3 on the summary table below.

4. Large Pre-B cell

The fourth stage of B cell development is characterized by M-chain in the pre-B receptor. This marker is expressed for the first time at this stage of B cell development. The re-arrangement of the VDJ genes also begins here.

Early B Cell Development Stages
The large pre-B cell is an early stage while the immature B cell is one of the late B Cell Development Stages (FrontiersIn)

Other markers that can help you identify this stage of the B cell development can be seen in the summary table on the last cell of the 4th row. They include the pre-BCR, CD19, and CD40 among others.

5. Small Pre-B cell

This is the 5th stage of B cell development in your body. As you can expect, it is more advanced compared to the previous stage. In this stage, there is continued re-arrangement of the VDJ genes. Your developing B cell will have V-J joining in this stage.

The developing B cell shrinks in size compared to the preceding stage. That is why this stage is called a small pre-B cell. There are other markers that can help you recognize that the developing B cells are at this 5th stage.

You can view a list of those markers in the summary table below, on the last cell of the 5th row.

6. Immature B cell

The immature B cell stage is the 6th step in the B cell development stages. Compared to the preceding 5th stage, this cell expresses a fully functional IgM that serves as the BCR (for recognition of antigens) for this stage.

For details about other markers expressed by your developing B cell in this stage, look at the last cell of the 6th row of the summary table below.

7. Mature B cell

The mature B cell stage is the most advanced stage of B cell development. This stage has more markers than any of the preceding stages. There is a final re-arrangement of the VDJ genes. In this stage, the mature B cell expresses both IgM and IgD as the B cell receptor.

Late B cell Development stages Image
Mature B cell is one of the latest B cell Development stages (FrontiersIn)

Your mature B cell will at this point have no expression of two markers that were earlier expressed in other stages. These two are RAG/TdT, and surrogate L-chain. You may look at the last cell of the mature B cell 7th row in the summary table below to see all the markers expressed in this stage.

Table showing Summary of B Cell Development Stages

Understanding the B cell Development Stages

Regulation of B cell Development

This process must be regulated to ensure the mature naïve B cells that will finally be released into your peripheral circulation are not harmful. Being harmful means that they can attack your own cells and destroy them (autoimmunity). That is obviously not what they are meant to do.

The B cells should only protect you against foreign bodies in an ideal situation. At the center of this regulation are two processes in your bone marrow. The positive selection and the negative selection.

Positive Selection of the Developing B cells

In positive selection, your developing B cells are selected for survival if the pre-B receptor binds its ligand successfully. What this means is that those B cells have receptors that can recognize and respond to foreign antigens.

These are considered helpful cells. The process of removal of inappropriate cells here is similar to what happens with the T cell development in the thymus.

Negative Selection of the Developing B cells

This involves the developing B cells that interact with your own cells in the bone marrow through their pre-B cell receptor. If they do so with high affinity, that means that those cells are potentially autoreactive (can cause autoimmunity).

They are killed to avert that situation in the future – what an intelligent system! Therefore, the B cells that inappropriately express their BCR like those expressing only IgM will be killed through apoptosis or clonal deletion.

Some B cells will only express enough IgD but very little amount of IgM. Those will become anergic (non-responsive) and later die. Your normal B cells should express both IgD and IgM as their BCRs.

If they do, they will be spared to go to the peripheral circulation as your naïve or resting B cells that are now ready to encounter an antigen, be activated, and become plasma cells begin to produce protective antibodies.  


The development of B cells in a normal human body goes through seven important stages. Each stage is characterized by several activities that make it unique and something that scientists can map in the laboratory.

That means it is possible to analyze your bone marrow sample or blood sample and tell how many B cells are in what stages of development. Yes, that is the far the scientific world has advanced. It has not been an easy journey though.

If the mature B cells are defective, the scientists can tell by demonstrating that they lack certain important markers and/or have abnormal markers.

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