3.2.2 Later antigen-dependent phase

The second phase of B-cell activation and final differentiation is dependent on selfantigens, then on non-self-antigens within the secondary lymphoid organs (SLOs). It results in the formation of plasma cells and antigenic specific memory B-cells.

#### Figure 6.

Phases of B-cell ontogeny. CLPs, common lymphoid progenitors; mIgM, membrane immunoglobulin M; DZ, dark zone; LZ, light zone; HLA, human leucocyte antigen; GC, germinal center; CSR, class switch recombination.

antigen–antibody complexes as well as in the selection of memory B-cells during GC reactions (GCRs) [33]. They contain naive B-cells, and adjacent to which are T-cell zones that form the periarteriolar lymphoid sheath (PALS). Phenotypically, they are IgM+/-IgD++, CD21+/, and CD23+, in mice.

3.2 Phases of B-cell ontogeny: antigen-dependent and antigen-independent

B-cell ontogeny can be separated into two main phases: earlier antigenindependent phase and later antigen-dependent phase (Figure 6). It should also be recalled that thymus-independent (TI) antigens have the ability to stimulate B-cells without T-cells' help and are traditionally divided into two categories, TI-1 antigens that can activate B-cells through coengagement of Toll-like receptors (TLR), such as LPS or other bacterial polysaccharides, and TI-2 antigens that lead to extensive cross-linking of the BCR, such as polymeric protein antigens or repeated structural motifs [33]. Some antigens fall outside these and form a third category. Finally, T-cell-independent responses should be discussed, knowing that T-cells could intervene at different levels of B-cell development in response to TI antigens (For

The first phase of B-cell differentiation and maturation would be antigenindependent. It takes place in the bone marrow and results in the generation of immature B-cells expressing pair L chains with μ chains to form cell surface monomeric IgM in association with transmembrane Igα and Igβ invariant chains, forming

The second phase of B-cell activation and final differentiation is dependent on selfantigens, then on non-self-antigens within the secondary lymphoid organs (SLOs). It results in the formation of plasma cells and antigenic specific memory B-cells.

Phases of B-cell ontogeny. CLPs, common lymphoid progenitors; mIgM, membrane immunoglobulin M; DZ, dark zone; LZ, light zone; HLA, human leucocyte antigen; GC, germinal center; CSR, class switch

the BCR complex, which is able to recognize and capture antigens.

review, see [34–36]).

Normal and Malignant B-cell

Figure 6.

14

recombination.

3.2.1 Earlier antigen-independent phase

3.2.2 Later antigen-dependent phase
